20-906268-G-C

Variant names:

• chr20-906268-G-C
• rs976166
• NM_015985.4:c.309+9638C>G

Variant summary

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

The NM_015985.4(ANGPT4):​c.309+9638C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,038 control chromosomes in the GnomAD database, including 6,455 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 0.28 (6455 hom., cov: 32)
• Consequence: ANGPT4 NM_015985.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.964

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANGPT4	NM_015985.4	c.309+9638C>G		intron_variant	Intron 1 of 8	ENST00000381922.5	NP_057069.1
ANGPT4	NM_001322809.2	c.309+9638C>G		intron_variant	Intron 1 of 7		NP_001309738.1
ANGPT4	XM_011529239.4	c.309+9638C>G		intron_variant	Intron 1 of 7		XP_011527541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANGPT4	ENST00000381922.5	c.309+9638C>G		intron_variant	Intron 1 of 8	1	NM_015985.4	ENSP00000371347.3

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43019 AN: 151920 Hom.: 6455 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.283 AC: 43014 AN: 152038 Hom.: 6455 Cov.: 32 AF XY: 0.283 AC XY: 21017 AN XY: 74310

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.258

Gnomad4 EAS AF: 0.512

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.246

Alfa AF: 0.138 Hom.: 253

Bravo AF: 0.274

Asia WGS AF: 0.431 AC: 1499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.67
DANN	Benign	0.40

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: rs976166; hg19: chr20-886911;