4-176686910-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005429.5(VEGFC):c.1145+277A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 151,972 control chromosomes in the GnomAD database, including 30,812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.63 (30812 hom., cov: 31)
• Consequence: VEGFC NM_005429.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.303

Genes affected

VEGFC (HGNC:12682): (vascular endothelial growth factor C) The protein encoded by this gene is a member of the platelet-derived growth factor/vascular endothelial growth factor (PDGF/VEGF) family. The encoded protein promotes angiogenesis and endothelial cell growth, and can also affect the permeability of blood vessels. The proprotein is further cleaved into a fully processed form that can bind and activate VEGFR-2 and VEGFR-3 receptors. [provided by RefSeq, Apr 2014]

HAFML (HGNC:56694): (HuR (ELAVL1) associated fibroblast migratory lncRNA)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 4-176686910-T-A is Benign according to our data. Variant chr4-176686910-T-A is described in ClinVar as [Benign]. Clinvar id is 1287592.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VEGFC	NM_005429.5	c.1145+277A>T		intron_variant		ENST00000618562.2
HAFML	NR_183975.1	n.182+17201T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VEGFC	ENST00000618562.2	c.1145+277A>T		intron_variant		1	NM_005429.5	P1
HAFML	ENST00000509194.1	n.89+17201T>A		intron_variant, non_coding_transcript_variant		3
HAFML	ENST00000504017.5	n.140+7160T>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95080 AN: 151854 Hom.: 30813 Cov.: 31

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.710

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.629

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.626 AC: 95119 AN: 151972 Hom.: 30812 Cov.: 31 AF XY: 0.634 AC XY: 47048 AN XY: 74266

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.597

Gnomad4 ASJ AF: 0.687

Gnomad4 EAS AF: 0.708

Gnomad4 SAS AF: 0.739

Gnomad4 FIN AF: 0.752

Gnomad4 NFE AF: 0.697

Gnomad4 OTH AF: 0.627

Alfa AF: 0.640 Hom.: 3934

Bravo AF: 0.604

Asia WGS AF: 0.706 AC: 2452 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.1
Dann	Benign	0.71

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: rs13142168; hg19: chr4-177608064;