Variant 14-74357767-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_018228.3(VRTN):c.984C>T(p.Gly328=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,613,010 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 20 hom. )

Consequence

VRTN
NM_018228.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.33

Variant links:

Genes affected

VRTN (HGNC:20223): (vertebrae development associated) Predicted to enable sequence-specific DNA binding activity and transposase activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in chromatin. [provided by Alliance of Genome Resources, Apr 2022]

VRTN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 14-74357767-C-T is Benign according to our data. Variant chr14-74357767-C-T is described in ClinVar as [Benign]. Clinvar id is 791039.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.33 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00102 (1492/1460642) while in subpopulation AMR AF= 0.0206 (922/44722). AF 95% confidence interval is 0.0195. There are 20 homozygotes in gnomad4_exome. There are 647 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VRTN	NM_018228.3 linkuse as main transcript	c.984C>T	p.Gly328=	synonymous_variant	2/2	ENST00000256362.5	NP_060698.2
VRTN	XM_011536911.3 linkuse as main transcript	c.984C>T	p.Gly328=	synonymous_variant	3/3		XP_011535213.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VRTN	ENST00000256362.5 linkuse as main transcript	c.984C>T	p.Gly328=	synonymous_variant	2/2	1	NM_018228.3	ENSP00000256362	P1

Frequencies

GnomAD3 genomes

AF:

0.00120

AC:

183

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00837

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00885

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00378

AC:

945

AN:

250078

Hom.:

AF XY:

0.00289

AC XY:

391

AN XY:

135390

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.0211

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.00949

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0000478

Gnomad NFE exome

AF:

0.0000618

Gnomad OTH exome

AF:

0.00229

GnomAD4 exome

AF:

0.00102

AC:

1492

AN:

1460642

Hom.:

Cov.:

AF XY:

0.000890

AC XY:

647

AN XY:

726698

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0206

Gnomad4 ASJ exome

AF:

0.00157

Gnomad4 EAS exome

AF:

0.0108

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.0000383

Gnomad4 NFE exome

AF:

0.0000288

Gnomad4 OTH exome

AF:

0.000729

GnomAD4 genome

AF:

0.00119

AC:

182

AN:

152368

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00830

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00887

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000425

Hom.:

Bravo

AF:

0.00222

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 15, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.77

DANN

Benign

0.45

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over