Genetic Variant B4GALNT1:c.*1859A>C (chr12-57624885-T-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001478.5(B4GALNT1):c.*1859A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00607 in 1,614,102 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0061 ( 34 hom. )

Consequence

B4GALNT1
NM_001478.5 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.75

Publications

11 publications found

Variant links:

Genes affected

B4GALNT1 (HGNC:4117): (beta-1,4-N-acetyl-galactosaminyltransferase 1) GM2 and GD2 gangliosides are sialic acid-containing glycosphingolipids. GalNAc-T is the enzyme involved in the biosynthesis of G(M2) and G(D2) glycosphingolipids. GalNAc-T catalyzes the transfer of GalNAc into G(M3) and G(D3) by a beta-1,4 linkage, resulting in the synthesis of G(M2) and G(D2), respectively. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2013]

B4GALNT1 links:

ENSG00000287908 (HGNC:):

ENSG00000287908 links:

SLC26A10P (HGNC:14470): (solute carrier family 26 member 10, pseudogene) Predicted to enable anion transmembrane transporter activity. Predicted to be involved in anion transport. Predicted to be active in basolateral plasma membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC26A10P links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.045810133).

BP6

Variant 12-57624885-T-G is Benign according to our data. Variant chr12-57624885-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2643143.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00589 (897/152238) while in subpopulation AMR AF = 0.00837 (128/15300). AF 95% confidence interval is 0.00719. There are 2 homozygotes in GnomAd4. There are 421 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001478.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
B4GALNT1	NM_001478.5	MANE Select	c.*1859A>C	3_prime_UTR	Exon 11 of 11	NP_001469.1	Q00973-1
B4GALNT1	NM_001413967.1		c.*1859A>C	3_prime_UTR	Exon 11 of 11	NP_001400896.1
B4GALNT1	NM_001413968.1		c.*1859A>C	3_prime_UTR	Exon 11 of 11	NP_001400897.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
B4GALNT1	ENST00000341156.9	TSL:1 MANE Select	c.*1859A>C	3_prime_UTR	Exon 11 of 11	ENSP00000341562.4	Q00973-1
ENSG00000287908	ENST00000474359.7	TSL:5	n.*1465T>G	non_coding_transcript_exon	Exon 18 of 23	ENSP00000431994.2	E9PIH7
ENSG00000287908	ENST00000474359.7	TSL:5	n.*1465T>G	3_prime_UTR	Exon 18 of 23	ENSP00000431994.2	E9PIH7

Frequencies

GnomAD3 genomes

AF:

0.00590

AC:

898

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00469

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.00838

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.00254

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00701

Gnomad OTH

AF:

0.00815

GnomAD2 exomes

AF:

0.00522

AC:

1312

AN:

251444

AF XY:

0.00530

show subpopulations

Gnomad AFR exome

AF:

0.00431

Gnomad AMR exome

AF:

0.00520

Gnomad ASJ exome

AF:

0.00486

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00268

Gnomad NFE exome

AF:

0.00730

Gnomad OTH exome

AF:

0.00734

GnomAD4 exome

AF:

0.00608

AC:

8893

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00601

AC XY:

4370

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.00385

AC:

129

AN:

33480

American (AMR)

AF:

0.00626

AC:

280

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00436

AC:

114

AN:

26134

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.00261

AC:

225

AN:

86258

European-Finnish (FIN)

AF:

0.00294

AC:

157

AN:

53420

Middle Eastern (MID)

AF:

0.0106

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00675

AC:

7511

AN:

1111984

Other (OTH)

AF:

0.00685

AC:

414

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

452

903

1355

1806

2258

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

274

548

822

1096

1370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00589

AC:

897

AN:

152238

Hom.:

Cov.:

AF XY:

0.00565

AC XY:

421

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.00467

AC:

194

AN:

41510

American (AMR)

AF:

0.00837

AC:

128

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00461

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00311

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00254

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00701

AC:

477

AN:

68018

Other (OTH)

AF:

0.00806

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

102

153

204

255

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00625

Hom.:

Bravo

AF:

0.00629

TwinsUK

AF:

0.00674

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.00409

AC:

ESP6500EA

AF:

0.00686

AC:

ExAC

AF:

0.00537

AC:

652

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00889

EpiControl

AF:

0.00806

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

0.030

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.27

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.72

M_CAP

Benign

0.080

MetaRNN

Benign

0.046

MetaSVM

Uncertain

0.39

MutationAssessor

Uncertain

2.7

PhyloP100

2.8

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.5

REVEL

Pathogenic

0.70

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.87

MVP

0.70

MPC

0.74

ClinPred

0.023

GERP RS

3.6

Varity_R

0.63

gMVP

0.75

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over