rs1426019461

Variant names:

• chr20-885102-C-G
• rs1426019461
• NM_015985.4:c.811G>C

Your query was ambiguous. Multiple possible variants found:

• chr20-885102-C-G
• chr20-885102-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015985.4(ANGPT4):​c.811G>C​(p.Glu271Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E271K) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: ANGPT4 NM_015985.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.305
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04768133).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015985.4. 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
	ANGPT4	NM_015985.4	MANE Select	c.811G>C	p.Glu271Gln	missense	Exon 4 of 9	NP_057069.1	Q9Y264-1
	ANGPT4	NM_001322809.2		c.811G>C	p.Glu271Gln	missense	Exon 4 of 8	NP_001309738.1	Q9Y264-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANGPT4	ENST00000381922.5	TSL:1 MANE Select	c.811G>C	p.Glu271Gln	missense	Exon 4 of 9	ENSP00000371347.3	Q9Y264-1
	ANGPT4	ENST00000878109.1		c.655G>C	p.Glu219Gln	missense	Exon 3 of 8	ENSP00000548168.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152212 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152212 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74360

African (AFR) AF: 0.00 AC: 0 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.2
DANN	Benign	0.55
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0053	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.035	N
PhyloP100		0.30
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.40	N
REVEL	Benign	0.032
Sift	Benign	0.71	T
Sift4G	Benign	0.58	T
Polyphen		0.0020	B
Vest4		0.18
MutPred		0.32		Gain of MoRF binding (P = 0.03)
MVP		0.32
MPC		0.19
ClinPred		0.037	T
GERP RS		-4.8
Varity_R		0.054
gMVP		0.29
Mutation Taster		=96/4	polymorphism

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: rs1426019461; hg19: chr20-865745;