rs596958

Positions:

• chr21-39651564-A-G
• chr21-39651564-A-T
• chr21-39651564-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001356336.2(B3GALT5):​c.-161+4942A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.955 in 152,344 control chromosomes in the GnomAD database, including 69,547 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.96 (69547 hom., cov: 34)
• Consequence: B3GALT5 NM_001356336.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.141

Genes affected

B3GALT5 (HGNC:920): (beta-1,3-galactosyltransferase 5) This gene encodes a member of a family of membrane-bound glycoproteins. The encoded protein may synthesize type 1 Lewis antigens, which are elevated in gastrointestinal and pancreatic cancers. Alternatively spliced transcript variants using multiple alternate promoters have been observed for this gene. [provided by RefSeq, Sep 2017]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.98 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
B3GALT5	NM_001356336.2	c.-161+4942A>G		intron_variant		ENST00000684187.2
B3GALT5	NM_001278650.2	c.-160-8189A>G		intron_variant
B3GALT5	NM_001356338.2	c.-161+4942A>G		intron_variant
B3GALT5	NM_001356339.2	c.-160-8189A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B3GALT5	ENST00000684187.2	c.-161+4942A>G		intron_variant			NM_001356336.2	P1
	ENST00000416555.1	n.220+21074A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.955 AC: 145377 AN: 152226 Hom.: 69490 Cov.: 34

Gnomad AFR AF: 0.988

Gnomad AMI AF: 0.971

Gnomad AMR AF: 0.918

Gnomad ASJ AF: 0.951

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.984

Gnomad FIN AF: 0.947

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.938

Gnomad OTH AF: 0.965

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.955 AC: 145494 AN: 152344 Hom.: 69547 Cov.: 34 AF XY: 0.956 AC XY: 71214 AN XY: 74496

Gnomad4 AFR AF: 0.988

Gnomad4 AMR AF: 0.918

Gnomad4 ASJ AF: 0.951

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.984

Gnomad4 FIN AF: 0.947

Gnomad4 NFE AF: 0.938

Gnomad4 OTH AF: 0.966

Alfa AF: 0.943 Hom.: 25555

Bravo AF: 0.954

Asia WGS AF: 0.991 AC: 3446 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.6
DANN	Benign	0.52

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

LitVar

Other links and lift over

dbSNP: rs596958; hg19: chr21-41023491;