rs4818065

Positions:

• chr21-39665796-A-G

Variant summary

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

The NM_001356336.2(B3GALT5):​c.*4304A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 152,222 control chromosomes in the GnomAD database, including 39,682 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 0.71 (39677 hom., cov: 33)
  • Exomes 𝑓: 0.86 (5 hom.)
• Consequence: B3GALT5 NM_001356336.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.498

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B3GALT5	NM_001356336.2	c.*4304A>G		3_prime_UTR_variant	4/4	ENST00000684187.2	NP_001343265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B3GALT5	ENST00000684187.2	c.*4304A>G		3_prime_UTR_variant	4/4		NM_001356336.2	ENSP00000506797	P1
B3GALT5	ENST00000380620.8	c.*4304A>G		3_prime_UTR_variant	5/5	1		ENSP00000369994	P1
	ENST00000416555.1	n.220+35306A>G		intron_variant, non_coding_transcript_variant		3
B3GALT5	ENST00000682818.1	n.607+2180A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107809 AN: 152090 Hom.: 39657 Cov.: 33

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.812

Gnomad FIN AF: 0.807

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.806

Gnomad OTH AF: 0.728

GnomAD4 exome AF: 0.857 AC: 12 AN: 14 Hom.: 5 Cov.: 0 AF XY: 1.00 AC XY: 6 AN XY: 6

Gnomad4 NFE exome AF: 0.917

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.709 AC: 107858 AN: 152208 Hom.: 39677 Cov.: 33 AF XY: 0.711 AC XY: 52929 AN XY: 74420

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.763

Gnomad4 ASJ AF: 0.791

Gnomad4 EAS AF: 0.665

Gnomad4 SAS AF: 0.811

Gnomad4 FIN AF: 0.807

Gnomad4 NFE AF: 0.806

Gnomad4 OTH AF: 0.730

Alfa AF: 0.731 Hom.: 7886

Bravo AF: 0.691

Asia WGS AF: 0.750 AC: 2610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.1
DANN	Benign	0.65

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: rs4818065; hg19: chr21-41037723;