Genetic Variant ENSG00000151303:n.3894C>T (chr10-87009537-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000444431.1(ENSG00000151303):n.3894C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000708 in 1,612,658 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00066 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00071 ( 3 hom. )

Consequence

ENSG00000151303
ENST00000444431.1 non_coding_transcript_exon

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.775

Variant links:

Genes affected

ENSG00000151303 (HGNC:):

ENSG00000151303 links:

AGAP11 (HGNC:29421): (ArfGAP with GTPase domain, ankyrin repeat and PH domain 11) Predicted to enable GTPase activator activity and metal ion binding activity. Predicted to be involved in regulation of catalytic activity. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

AGAP11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 10-87009537-C-T is Benign according to our data. Variant chr10-87009537-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2346886.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGAP11	NR_171046.1 link	n.2793C>T		non_coding_transcript_exon_variant	Exon 11 of 11

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ENSG00000151303	ENST00000444431.1 link	n.3894C>T	non_coding_transcript_exon_variant	Exon 7 of 7	1
ENSG00000271880	ENST00000433214.2 link	n.2489C>T	non_coding_transcript_exon_variant	Exon 12 of 12	2
AGAP11	ENST00000437689.3 link	n.1372C>T	non_coding_transcript_exon_variant	Exon 4 of 4	6

Frequencies

GnomAD3 genomes

AF:

0.000665

AC:

101

AN:

151820

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000487

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

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:

0.000705

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000518

AC:

130

AN:

251134

Hom.:

AF XY:

0.000442

AC XY:

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.000623

Gnomad AMR exome

AF:

0.00124

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000598

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000713

AC:

1041

AN:

1460720

Hom.:

Cov.:

AF XY:

0.000665

AC XY:

483

AN XY:

726708

show subpopulations

Gnomad4 AFR exome

AF:

0.000300

Gnomad4 AMR exome

AF:

0.000939

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000290

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000818

Gnomad4 OTH exome

AF:

0.000713

GnomAD4 genome

AF:

0.000658

AC:

100

AN:

151938

Hom.:

Cov.:

AF XY:

0.000619

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.000485

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000706

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000508

Hom.:

Bravo

AF:

0.000842

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Sep 22, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

1.6

DANN

Benign

0.63

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over