rs6077309

Positions:

• chr20-882180-G-A
• chr20-882180-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015985.4(ANGPT4):​c.836-894C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,050 control chromosomes in the GnomAD database, including 5,611 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (5611 hom., cov: 32)
• Consequence: ANGPT4 NM_015985.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132

Genes affected

ANGPT4 (HGNC:487): (angiopoietin 4) Angiopoietins are proteins with important roles in vascular development and angiogenesis. All angiopoietins bind with similar affinity to an endothelial cell-specific tyrosine-protein kinase receptor. The mechanism by which they contribute to angiogenesis is thought to involve regulation of endothelial cell interactions with supporting perivascular cells. The protein encoded by this gene functions as an agonist and is an angiopoietin. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANGPT4	NM_015985.4	c.836-894C>T		intron_variant		ENST00000381922.5	NP_057069.1
ANGPT4	NM_001322809.2	c.836-894C>T		intron_variant			NP_001309738.1
ANGPT4	XM_011529239.4	c.680-894C>T		intron_variant			XP_011527541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANGPT4	ENST00000381922.5	c.836-894C>T		intron_variant		1	NM_015985.4	ENSP00000371347	P1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36964 AN: 151932 Hom.: 5593 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.243 AC: 37024 AN: 152050 Hom.: 5611 Cov.: 32 AF XY: 0.245 AC XY: 18236 AN XY: 74322

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.224

Alfa AF: 0.164 Hom.: 3009

Bravo AF: 0.255

Asia WGS AF: 0.226 AC: 786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.2
DANN	Benign	0.61

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: rs6077309; hg19: chr20-862823;