chr19-17807939-C-T

Variant names:

• chr19-17807939-C-T
• rs79614823
• NM_014256.4:c.132C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_014256.4(B3GNT3):​c.132C>T​(p.Pro44Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,613,396 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0058 (7 hom., cov: 30)
  • Exomes 𝑓: 0.00062 (10 hom.)
• Consequence: B3GNT3 NM_014256.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.16

Genes affected

B3GNT3 (HGNC:13528): (UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 3) This gene encodes a member of the beta-1,3-N-acetylglucosaminyltransferase family. This enzyme is a type II transmembrane protein and contains a signal anchor that is not cleaved. It prefers the substrates of lacto-N-tetraose and lacto-N-neotetraose, and is involved in the biosynthesis of poly-N-acetyllactosamine chains and the biosynthesis of the backbone structure of dimeric sialyl Lewis a. It plays dominant roles in L-selectin ligand biosynthesis, lymphocyte homing and lymphocyte trafficking. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 19-17807939-C-T is Benign according to our data. Variant chr19-17807939-C-T is described in ClinVar as [Benign]. Clinvar id is 769962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.16 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00578 (880/152202) while in subpopulation AFR AF = 0.0205 (851/41520). AF 95% confidence interval is 0.0194. There are 7 homozygotes in GnomAd4. There are 422 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GNT3	NM_014256.4	c.132C>T	p.Pro44Pro	synonymous_variant	Exon 2 of 3	ENST00000318683.7	NP_055071.2
B3GNT3	XM_011527626.3	c.132C>T	p.Pro44Pro	synonymous_variant	Exon 2 of 3		XP_011525928.1
B3GNT3	XM_047438042.1	c.132C>T	p.Pro44Pro	synonymous_variant	Exon 2 of 3		XP_047293998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B3GNT3	ENST00000318683.7	c.132C>T	p.Pro44Pro	synonymous_variant	Exon 2 of 3	1	NM_014256.4	ENSP00000321874.5
B3GNT3	ENST00000595387.1	c.132C>T	p.Pro44Pro	synonymous_variant	Exon 2 of 3	1		ENSP00000472638.1
B3GNT3	ENST00000599265.5	c.132C>T	p.Pro44Pro	synonymous_variant	Exon 2 of 3	3		ENSP00000471733.1
B3GNT3	ENST00000600777.1	c.132C>T	p.Pro44Pro	synonymous_variant	Exon 2 of 2	3		ENSP00000468914.1

Frequencies

GnomAD3 genomes AF: 0.00575 AC: 875 AN: 152084 Hom.: 7 Cov.: 30

Gnomad AFR AF: 0.0204

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00240

GnomAD2 exomes AF: 0.00167 AC: 414 AN: 248140 AF XY: 0.00119

Gnomad AFR exome AF: 0.0206

Gnomad AMR exome AF: 0.00104

Gnomad ASJ exome AF: 0.00250

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000807

Gnomad OTH exome AF: 0.00346

GnomAD4 exome AF: 0.000625 AC: 913 AN: 1461194 Hom.: 10 Cov.: 30 AF XY: 0.000537 AC XY: 390 AN XY: 726916

Gnomad4 AFR exome AF: 0.0206 AC: 691 AN: 33474

Gnomad4 AMR exome AF: 0.000984 AC: 44 AN: 44724

Gnomad4 ASJ exome AF: 0.00218 AC: 57 AN: 26122

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39694

Gnomad4 SAS exome AF: 0.0000348 AC: 3 AN: 86248

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 52894

Gnomad4 NFE exome AF: 0.00000809 AC: 9 AN: 1111898

Gnomad4 Remaining exome AF: 0.00113 AC: 68 AN: 60372

GnomAD4 genome AF: 0.00578 AC: 880 AN: 152202 Hom.: 7 Cov.: 30 AF XY: 0.00567 AC XY: 422 AN XY: 74410

Gnomad4 AFR AF: 0.0205 AC: 0.0204961 AN: 0.0204961

Gnomad4 AMR AF: 0.00105 AC: 0.00104698 AN: 0.00104698

Gnomad4 ASJ AF: 0.00144 AC: 0.00144092 AN: 0.00144092

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.0000294 AC: 0.0000294048 AN: 0.0000294048

Gnomad4 OTH AF: 0.00237 AC: 0.00237192 AN: 0.00237192

Alfa AF: 0.00378 Hom.: 4

Bravo AF: 0.00651

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.2
DANN	Benign	0.61
Mutation Taster		=100/0	polymorphism

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: rs79614823; hg19: chr19-17918748; COSMIC: COSV59437415;