Genetic Variant B4GALNT2:p.Phe55Leu (chr17-49133190-T-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_153446.3(B4GALNT2):c.165T>G(p.Phe55Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000179 in 1,507,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000074 ( 0 hom. )

Consequence

B4GALNT2
NM_153446.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.109

Publications

0 publications found

Variant links:

Genes affected

B4GALNT2 (HGNC:24136): (beta-1,4-N-acetyl-galactosaminyltransferase 2 (SID blood group)) B4GALNT2 catalyzes the last step in the biosynthesis of the human Sd(a) antigen through the addition of an N-acetylgalactosamine residue via a beta-1,4 linkage to a subterminal galactose residue substituted with an alpha-2,3-linked sialic acid. B4GALNT2 also catalyzes the last step in the biosynthesis of the Cad antigen (Montiel et al., 2003 [PubMed 12678917]).[supplied by OMIM, Mar 2008]

B4GALNT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06610456).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153446.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
B4GALNT2	NM_001159387.2	MANE Select	c.14+384T>G		intron	N/A	NP_001152859.1	Q8NHY0-2
B4GALNT2	NM_153446.3		c.165T>G	p.Phe55Leu	missense	Exon 1 of 11	NP_703147.2	Q8NHY0-1
B4GALNT2	NM_001159388.2		c.-65+680T>G		intron	N/A	NP_001152860.1	Q8NHY0-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
B4GALNT2	ENST00000300404.2	TSL:1	c.165T>G	p.Phe55Leu	missense	Exon 1 of 11	ENSP00000300404.2	Q8NHY0-1
B4GALNT2	ENST00000393354.7	TSL:1 MANE Select	c.14+384T>G		intron	N/A	ENSP00000377022.3	Q8NHY0-2
B4GALNT2	ENST00000954078.1		c.14+384T>G		intron	N/A	ENSP00000624137.1

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

151954

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000435

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000906

AC:

AN:

110378

AF XY:

0.0000162

show subpopulations

Gnomad AFR exome

AF:

0.000291

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000738

AC:

AN:

1355674

Hom.:

Cov.:

AF XY:

0.00000896

AC XY:

AN XY:

669812

show subpopulations

African (AFR)

AF:

0.000328

AC:

AN:

27442

American (AMR)

AF:

0.00

AC:

AN:

26022

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23806

East Asian (EAS)

AF:

0.00

AC:

AN:

30384

South Asian (SAS)

AF:

0.00

AC:

AN:

74016

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47922

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4674

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1065428

Other (OTH)

AF:

0.0000179

AC:

AN:

55980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000112

AC:

AN:

152072

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.000410

AC:

AN:

41500

American (AMR)

AF:

0.00

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5114

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67962

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000154

Hom.:

Bravo

AF:

0.000185

ESP6500AA

AF:

0.000487

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000179

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.54

CADD

Benign

7.5

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.044

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.32

M_CAP

Benign

0.0016

MetaRNN

Benign

0.066

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

-0.11

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.19

REVEL

Benign

0.085

Sift

Benign

0.15

Sift4G

Benign

0.78

Polyphen

0.72

Vest4

0.21

MutPred

0.30

Gain of helix (P = 0.0854)

MVP

0.35

MPC

0.24

ClinPred

0.062

GERP RS

-0.26

PromoterAI

0.029

Neutral

(source)

Varity_R

0.085

gMVP

0.18

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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