17-49132804-C-A

Variant names:

• chr17-49132804-C-A
• rs146443714
• NM_001159387.2:c.12C>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001159387.2(B4GALNT2):​c.12C>A​(p.Gly4Gly) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00989 in 1,375,652 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0062 (6 hom., cov: 31)
  • Exomes 𝑓: 0.010 (97 hom.)
• Consequence: B4GALNT2 NM_001159387.2 splice_region, synonymous
• Scores: Splicing: ADA: 0.0001619
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0340
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 17-49132804-C-A is Benign according to our data. Variant chr17-49132804-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2647886.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.034 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 6 BG gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001159387.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B4GALNT2	NM_001159387.2	MANE Select	c.12C>A	p.Gly4Gly	splice_region synonymous	Exon 1 of 11	NP_001152859.1	Q8NHY0-2
	B4GALNT2	NM_153446.3		c.-222C>A		5_prime_UTR	Exon 1 of 11	NP_703147.2	Q8NHY0-1
	B4GALNT2	NM_001159388.2		c.-65+294C>A		intron	N/A	NP_001152860.1	Q8NHY0-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B4GALNT2	ENST00000393354.7	TSL:1 MANE Select	c.12C>A	p.Gly4Gly	splice_region synonymous	Exon 1 of 11	ENSP00000377022.3	Q8NHY0-2
	B4GALNT2	ENST00000954078.1		c.12C>A	p.Gly4Gly	splice_region synonymous	Exon 1 of 12	ENSP00000624137.1
	B4GALNT2	ENST00000888693.1		c.12C>A	p.Gly4Gly	splice_region synonymous	Exon 1 of 10	ENSP00000558752.1

Frequencies

GnomAD3 genomes AF: 0.00620 AC: 943 AN: 152072 Hom.: 6 Cov.: 31

Gnomad AFR AF: 0.00193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00589

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00684

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00993

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00541 AC: 154 AN: 28466 AF XY: 0.00530

Gnomad AFR exome AF: 0.000636

Gnomad AMR exome AF: 0.000700

Gnomad ASJ exome AF: 0.00560

Gnomad EAS exome AF: 0.00120

Gnomad FIN exome AF: 0.00278

Gnomad NFE exome AF: 0.00921

Gnomad OTH exome AF: 0.00810

GnomAD4 exome AF: 0.0104 AC: 12667 AN: 1223462 Hom.: 97 Cov.: 30 AF XY: 0.0100 AC XY: 5918 AN XY: 590832

African (AFR) AF: 0.00134 AC: 32 AN: 23926

American (AMR) AF: 0.00395 AC: 42 AN: 10642

Ashkenazi Jewish (ASJ) AF: 0.00952 AC: 163 AN: 17124

East Asian (EAS) AF: 0.00 AC: 0 AN: 27370

South Asian (SAS) AF: 0.00406 AC: 204 AN: 50298

European-Finnish (FIN) AF: 0.00257 AC: 114 AN: 44330

Middle Eastern (MID) AF: 0.00268 AC: 13 AN: 4842

European-Non Finnish (NFE) AF: 0.0116 AC: 11577 AN: 994914

Other (OTH) AF: 0.0104 AC: 522 AN: 50016

GnomAD4 genome AF: 0.00619 AC: 942 AN: 152190 Hom.: 6 Cov.: 31 AF XY: 0.00562 AC XY: 418 AN XY: 74406

African (AFR) AF: 0.00193 AC: 80 AN: 41518

American (AMR) AF: 0.00589 AC: 90 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00836 AC: 29 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00664 AC: 32 AN: 4818

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00993 AC: 675 AN: 68002

Other (OTH) AF: 0.0104 AC: 22 AN: 2116

Alfa AF: 0.00484 Hom.: 1

Bravo AF: 0.00606

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	13
DANN	Benign	0.89
PhyloP100		-0.034
PromoterAI		-0.0030	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00016
dbscSNV1_RF	Benign	0.0080

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

Other links and lift over

dbSNP: rs146443714; hg19: chr17-47210166;