14-74303274-G-A

Position:

• chr14-74303274-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000557177.1(VRTN):​c.-164+98G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 208,518 control chromosomes in the GnomAD database, including 10,900 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7255 hom., cov: 33)
  • Exomes 𝑓: 0.35 (3645 hom.)
• Consequence: VRTN ENST00000557177.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.586

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 14-74303274-G-A is Benign according to our data. Variant chr14-74303274-G-A is described in ClinVar as [Benign]. Clinvar id is 1234864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VRTN	XM_011536911.3	c.-164+124G>A		intron_variant			XP_011535213.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VRTN	ENST00000557177.1	c.-164+98G>A		intron_variant		4		ENSP00000452158

Frequencies

GnomAD3 genomes AF: 0.296 AC: 45087 AN: 152082 Hom.: 7263 Cov.: 33

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.354

GnomAD4 exome AF: 0.350 AC: 19689 AN: 56318 Hom.: 3645 AF XY: 0.349 AC XY: 9855 AN XY: 28244

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.271

Gnomad4 ASJ exome AF: 0.428

Gnomad4 EAS exome AF: 0.230

Gnomad4 SAS exome AF: 0.363

Gnomad4 FIN exome AF: 0.304

Gnomad4 NFE exome AF: 0.375

Gnomad4 OTH exome AF: 0.357

GnomAD4 genome AF: 0.296 AC: 45079 AN: 152200 Hom.: 7255 Cov.: 33 AF XY: 0.294 AC XY: 21868 AN XY: 74398

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.359

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.354

Alfa AF: 0.298 Hom.: 1038

Bravo AF: 0.288

Asia WGS AF: 0.307 AC: 1065 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	GeneDx	Jul 07, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.9
DANN	Benign	0.58

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs67772080; hg19: chr14-74769977;