chr4-176687621-T-C

Variant names:

• chr4-176687621-T-C
• rs4604006
• NM_005429.5:c.812-101A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005429.5(VEGFC):​c.812-101A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 1,228,454 control chromosomes in the GnomAD database, including 286,949 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (28364 hom., cov: 33)
  • Exomes 𝑓: 0.69 (258585 hom.)
• Consequence: VEGFC NM_005429.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.767
• Publications: 28 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 4-176687621-T-C is Benign according to our data. Variant chr4-176687621-T-C is described in ClinVar as Benign. ClinVar VariationId is 1231039.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005429.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEGFC	NM_005429.5	MANE Select	c.812-101A>G		intron	N/A	NP_005420.1	P49767
	HAFML	NR_183975.1		n.182+17912T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEGFC	ENST00000618562.2	TSL:1 MANE Select	c.812-101A>G		intron	N/A	ENSP00000480043.1	P49767
	HAFML	ENST00000504017.6	TSL:2	n.243+7871T>C		intron	N/A
	HAFML	ENST00000509194.2	TSL:3	n.155+17912T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.586 AC: 89077 AN: 151962 Hom.: 28374 Cov.: 33

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.600

GnomAD4 exome AF: 0.689 AC: 742022 AN: 1076374 Hom.: 258585 Cov.: 14 AF XY: 0.691 AC XY: 366748 AN XY: 530442

African (AFR) AF: 0.311 AC: 7459 AN: 23970

American (AMR) AF: 0.574 AC: 11064 AN: 19274

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 11836 AN: 17594

East Asian (EAS) AF: 0.701 AC: 23745 AN: 33880

South Asian (SAS) AF: 0.735 AC: 41480 AN: 56404

European-Finnish (FIN) AF: 0.727 AC: 24917 AN: 34284

Middle Eastern (MID) AF: 0.651 AC: 2138 AN: 3282

European-Non Finnish (NFE) AF: 0.699 AC: 588275 AN: 841126

Other (OTH) AF: 0.668 AC: 31108 AN: 46560

GnomAD4 genome AF: 0.586 AC: 89089 AN: 152080 Hom.: 28364 Cov.: 33 AF XY: 0.595 AC XY: 44255 AN XY: 74354

African (AFR) AF: 0.321 AC: 13297 AN: 41474

American (AMR) AF: 0.583 AC: 8911 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.675 AC: 2341 AN: 3470

East Asian (EAS) AF: 0.706 AC: 3654 AN: 5176

South Asian (SAS) AF: 0.737 AC: 3556 AN: 4824

European-Finnish (FIN) AF: 0.752 AC: 7951 AN: 10580

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.696 AC: 47286 AN: 67954

Other (OTH) AF: 0.598 AC: 1264 AN: 2112

Alfa AF: 0.556 Hom.: 6960

Bravo AF: 0.559

Asia WGS AF: 0.700 AC: 2432 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.8
DANN	Benign	0.39
PhyloP100		-0.77
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4604006; hg19: chr4-177608775;