Variant 7-102605955-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000262940.12(RASA4):c.331G>A(p.Asp111Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00054 in 151,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00054 ( 0 hom., cov: 70)

Exomes 𝑓: 0.00024 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

RASA4
ENST00000262940.12 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.22

Variant links:

Genes affected

RASA4 (HGNC:23181): (RAS p21 protein activator 4) This gene encodes a member of the GAP1 family of GTPase-activating proteins that suppresses the Ras/mitogen-activated protein kinase pathway in response to Ca(2+). Stimuli that increase intracellular Ca(2+) levels result in the translocation of this protein to the plasma membrane, where it activates Ras GTPase activity. Consequently, Ras is converted from the active GTP-bound state to the inactive GDP-bound state and no longer activates downstream pathways that regulate gene expression, cell growth, and differentiation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

RASA4 links:

ENSG00000205236 (HGNC:):

ENSG00000205236 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13174713).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASA4	NM_006989.6 linkuse as main transcript	c.331G>A	p.Asp111Asn	missense_variant	5/21	ENST00000262940.12	NP_008920.5	O43374-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RASA4	ENST00000262940.12 linkuse as main transcript	c.331G>A	p.Asp111Asn	missense_variant	5/21	1	NM_006989.6	ENSP00000262940.8	O43374-1
ENSG00000205236	ENST00000519541.1 linkuse as main transcript	n.*221G>A		non_coding_transcript_exon_variant	10/26	2		ENSP00000429397.1	A0A286YEE6
ENSG00000205236	ENST00000519541.1 linkuse as main transcript	n.*221G>A		3_prime_UTR_variant	10/26	2		ENSP00000429397.1	A0A286YEE6

Frequencies

GnomAD3 genomes

AF:

0.000533

AC:

AN:

151848

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000558

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000525

Gnomad ASJ

AF:

0.00379

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00325

Gnomad NFE

AF:

0.000427

Gnomad OTH

AF:

0.00144

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000237

AC:

345

AN:

1454704

Hom.:

Cov.:

110

AF XY:

0.000257

AC XY:

186

AN XY:

723408

show subpopulations

Gnomad4 AFR exome

AF:

0.000541

Gnomad4 AMR exome

AF:

0.000293

Gnomad4 ASJ exome

AF:

0.00280

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000560

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000132

Gnomad4 OTH exome

AF:

0.000651

GnomAD4 genome

AF:

0.000540

AC:

AN:

151966

Hom.:

Cov.:

AF XY:

0.000484

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.000580

Gnomad4 AMR

AF:

0.000524

Gnomad4 ASJ

AF:

0.00379

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000427

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00103

Hom.:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.000323

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 22, 2021

The c.331G>A (p.D111N) alteration is located in exon 5 (coding exon 5) of the RASA4 gene. This alteration results from a G to A substitution at nucleotide position 331, causing the aspartic acid (D) at amino acid position 111 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.46

T;T;.;T;.;.

Eigen

Uncertain

0.32

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.91

D;.;D;D;D;D

M_CAP

Benign

0.070

MetaRNN

Benign

0.13

T;T;T;T;T;T

MetaSVM

Uncertain

-0.26

MutationAssessor

Uncertain

2.3

M;.;M;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-2.9

D;D;D;D;D;D

REVEL

Benign

0.24

Sift

Benign

0.056

T;T;T;T;T;T

Sift4G

Uncertain

0.018

D;D;D;D;D;T

Polyphen

1.0

D;.;D;.;.;.

Vest4

0.31

MVP

0.80

MPC

2.7

ClinPred

0.18

GERP RS

1.8

Varity_R

0.25

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

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