21-39659683-C-T

Variant names:

• chr21-39659683-C-T
• rs2837108
• NM_001356336.2:c.-160-70C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001356336.2(B3GALT5):​c.-160-70C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 884,472 control chromosomes in the GnomAD database, including 85,051 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 0.35 (10961 hom., cov: 31)
  • Exomes 𝑓: 0.44 (74090 hom.)
• Consequence: B3GALT5 NM_001356336.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114
• Publications: 9 publications found

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]

ENSG00000225330 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GALT5	NM_001356336.2	c.-160-70C>T		intron_variant	Intron 2 of 3	ENST00000684187.2	NP_001343265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B3GALT5	ENST00000684187.2	c.-160-70C>T		intron_variant	Intron 2 of 3		NM_001356336.2	ENSP00000506797.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52570 AN: 151400 Hom.: 10961 Cov.: 31

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.0760

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.385

GnomAD4 exome AF: 0.445 AC: 325909 AN: 733004 Hom.: 74090 AF XY: 0.446 AC XY: 152240 AN XY: 341268

African (AFR) AF: 0.0976 AC: 1344 AN: 13766

American (AMR) AF: 0.334 AC: 287 AN: 860

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 2371 AN: 4556

East Asian (EAS) AF: 0.0769 AC: 244 AN: 3172

South Asian (SAS) AF: 0.434 AC: 6248 AN: 14408

European-Finnish (FIN) AF: 0.400 AC: 100 AN: 250

Middle Eastern (MID) AF: 0.483 AC: 701 AN: 1452

European-Non Finnish (NFE) AF: 0.454 AC: 304553 AN: 670632

Other (OTH) AF: 0.421 AC: 10061 AN: 23908

GnomAD4 genome AF: 0.347 AC: 52571 AN: 151468 Hom.: 10961 Cov.: 31 AF XY: 0.351 AC XY: 25941 AN XY: 73948

African (AFR) AF: 0.129 AC: 5297 AN: 41180

American (AMR) AF: 0.374 AC: 5696 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1804 AN: 3466

East Asian (EAS) AF: 0.0756 AC: 389 AN: 5148

South Asian (SAS) AF: 0.426 AC: 2042 AN: 4798

European-Finnish (FIN) AF: 0.460 AC: 4799 AN: 10426

Middle Eastern (MID) AF: 0.524 AC: 152 AN: 290

European-Non Finnish (NFE) AF: 0.458 AC: 31098 AN: 67924

Other (OTH) AF: 0.383 AC: 804 AN: 2098

Alfa AF: 0.425 Hom.: 26633

Bravo AF: 0.327

Asia WGS AF: 0.264 AC: 918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.8
DANN	Benign	0.69
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2837108; hg19: chr21-41031610;