Variant 2-237817811-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001080504.3(RBM44):c.892G>A(p.Val298Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RBM44
NM_001080504.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.748

Variant links:

Genes affected

RBM44 (HGNC:24756): (RNA binding motif protein 44) Predicted to enable protein homodimerization activity. Predicted to be located in cytoplasm and intercellular bridge. [provided by Alliance of Genome Resources, Apr 2022]

RBM44 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05078107).

BP6

Variant 2-237817811-G-A is Benign according to our data. Variant chr2-237817811-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2238060.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM44	NM_001080504.3 linkuse as main transcript	c.892G>A	p.Val298Ile	missense_variant	3/16	ENST00000316997.9	NP_001073973.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
RBM44	ENST00000316997.9 linkuse as main transcript	c.892G>A	p.Val298Ile	missense_variant	3/16	5	NM_001080504.3	ENSP00000321179	P1
RBM44	ENST00000409864.6 linkuse as main transcript	c.892G>A	p.Val298Ile	missense_variant	3/15	5		ENSP00000386727	P1
RBM44	ENST00000480583.5 linkuse as main transcript	n.1383G>A		non_coding_transcript_exon_variant	3/15	2
RBM44	ENST00000444524.2 linkuse as main transcript	n.202-2364G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000810

AC:

AN:

247040

Hom.:

AF XY:

0.00000746

AC XY:

AN XY:

134042

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000895

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460072

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726314

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 16, 2021

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

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.38

DANN

Benign

0.76

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.42

T;.

M_CAP

Benign

0.0037

MetaRNN

Benign

0.051

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.26

N;N

REVEL

Benign

0.020

Sift

Benign

0.34

T;T

Sift4G

Benign

0.42

T;T

Vest4

0.036

MVP

0.20

MPC

0.020

ClinPred

0.089

GERP RS

-10

gMVP

0.017

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

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