17-49132804-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001159387.2(B4GALNT2):​c.12C>T​(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 0.00000572 in 1,223,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G4G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000057 (0 hom.)
• Consequence: B4GALNT2 NM_001159387.2 splice_region, synonymous
• Scores: Splicing: ADA: 0.0001578
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=-0.034 with no splicing effect.

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>T	p.Gly4Gly	splice_region synonymous	Exon 1 of 11	NP_001152859.1	Q8NHY0-2
	B4GALNT2	NM_153446.3		c.-222C>T		5_prime_UTR	Exon 1 of 11	NP_703147.2	Q8NHY0-1
	B4GALNT2	NM_001159388.2		c.-65+294C>T		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>T	p.Gly4Gly	splice_region synonymous	Exon 1 of 11	ENSP00000377022.3	Q8NHY0-2
	B4GALNT2	ENST00000954078.1		c.12C>T	p.Gly4Gly	splice_region synonymous	Exon 1 of 12	ENSP00000624137.1
	B4GALNT2	ENST00000888693.1		c.12C>T	p.Gly4Gly	splice_region synonymous	Exon 1 of 10	ENSP00000558752.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000572 AC: 7 AN: 1223484 Hom.: 0 Cov.: 30 AF XY: 0.00000677 AC XY: 4 AN XY: 590844

African (AFR) AF: 0.00 AC: 0 AN: 23926

American (AMR) AF: 0.00 AC: 0 AN: 10642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17124

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

South Asian (SAS) AF: 0.0000994 AC: 5 AN: 50298

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4842

European-Non Finnish (NFE) AF: 0.00000101 AC: 1 AN: 994934

Other (OTH) AF: 0.0000200 AC: 1 AN: 50018

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Benign	0.94
PhyloP100		-0.034
PromoterAI		-0.024	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00016
dbscSNV1_RF	Benign	0.020

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

Other links and lift over

dbSNP: rs146443714; hg19: chr17-47210166;