rs13136065

Variant names:

• chr4-176688049-G-A
• rs13136065
• NM_005429.5:c.705-122C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-176688049-G-A
• chr4-176688049-G-C

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.705-122C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 538,242 control chromosomes in the GnomAD database, including 118,369 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (28326 hom., cov: 32)
  • Exomes 𝑓: 0.68 (90043 hom.)
• Consequence: VEGFC NM_005429.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.503
• Publications: 1 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=-0.9).
• BP6: Variant 4-176688049-G-A is Benign according to our data. Variant chr4-176688049-G-A is described in ClinVar as Benign. ClinVar VariationId is 1250186.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.705-122C>T		intron	N/A	NP_005420.1	P49767
	HAFML	NR_183975.1		n.183-17854G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEGFC	ENST00000618562.2	TSL:1 MANE Select	c.705-122C>T		intron	N/A	ENSP00000480043.1	P49767
	HAFML	ENST00000504017.6	TSL:2	n.243+8299G>A		intron	N/A
	HAFML	ENST00000509194.2	TSL:3	n.156-17854G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.586 AC: 89016 AN: 151888 Hom.: 28336 Cov.: 32

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.601

GnomAD4 exome AF: 0.678 AC: 261926 AN: 386236 Hom.: 90043 AF XY: 0.681 AC XY: 136314 AN XY: 200274

African (AFR) AF: 0.313 AC: 3087 AN: 9872

American (AMR) AF: 0.561 AC: 6465 AN: 11524

Ashkenazi Jewish (ASJ) AF: 0.666 AC: 7758 AN: 11642

East Asian (EAS) AF: 0.686 AC: 17965 AN: 26176

South Asian (SAS) AF: 0.708 AC: 18086 AN: 25548

European-Finnish (FIN) AF: 0.728 AC: 27181 AN: 37320

Middle Eastern (MID) AF: 0.647 AC: 2134 AN: 3298

European-Non Finnish (NFE) AF: 0.691 AC: 164595 AN: 238208

Other (OTH) AF: 0.647 AC: 14655 AN: 22648

GnomAD4 genome AF: 0.586 AC: 89028 AN: 152006 Hom.: 28326 Cov.: 32 AF XY: 0.595 AC XY: 44201 AN XY: 74292

African (AFR) AF: 0.320 AC: 13277 AN: 41430

American (AMR) AF: 0.582 AC: 8892 AN: 15270

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

East Asian (EAS) AF: 0.702 AC: 3633 AN: 5176

South Asian (SAS) AF: 0.737 AC: 3552 AN: 4818

European-Finnish (FIN) AF: 0.752 AC: 7941 AN: 10566

Middle Eastern (MID) AF: 0.613 AC: 179 AN: 292

European-Non Finnish (NFE) AF: 0.696 AC: 47300 AN: 67960

Other (OTH) AF: 0.599 AC: 1265 AN: 2112

Alfa AF: 0.616 Hom.: 3763

Bravo AF: 0.559

Asia WGS AF: 0.699 AC: 2422 AN: 3472

ClinVar

ClinVar submissions as Germline

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	-0.90
CADD	Benign	5.5
DANN	Benign	0.47
PhyloP100		0.50
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: rs13136065; hg19: chr4-177609203;