Variant 11-60302703-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_148975.3(MS4A4A):c.532A>G(p.Met178Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 1,611,886 control chromosomes in the GnomAD database, including 71,367 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.29 ( 6797 hom., cov: 32)

Exomes 𝑓: 0.29 ( 64570 hom. )

Consequence

MS4A4A
NM_148975.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -4.37

Variant links:

Genes affected

MS4A4A (HGNC:13371): (membrane spanning 4-domains A4A) This gene encodes a member of the membrane-spanning 4A gene family. Members of this nascent protein family are characterized by common structural features, similar intron/exon splice boundaries, and display unique expression patterns in hematopoietic cells and nonlymphoid tissues. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

MS4A4A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00714615).

BP6

Variant 11-60302703-A-G is Benign according to our data. Variant chr11-60302703-A-G is described in ClinVar as [Benign]. Clinvar id is 1223746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MS4A4A	NM_148975.3 linkuse as main transcript	c.532A>G	p.Met178Val	missense_variant	5/7	ENST00000337908.5
MS4A4A	NM_024021.4 linkuse as main transcript	c.475A>G	p.Met159Val	missense_variant	6/8
MS4A4A	NM_001243266.2 linkuse as main transcript	c.387+1646A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MS4A4A	ENST00000337908.5 linkuse as main transcript	c.532A>G	p.Met178Val	missense_variant	5/7	1	NM_148975.3	A2	Q96JQ5-1

Frequencies

GnomAD3 genomes

AF:

0.295

AC:

44800

AN:

152026

Hom.:

6797

Cov.:

show subpopulations

Gnomad AFR

AF:

0.313

Gnomad AMI

AF:

0.420

Gnomad AMR

AF:

0.243

Gnomad ASJ

AF:

0.377

Gnomad EAS

AF:

0.381

Gnomad SAS

AF:

0.343

Gnomad FIN

AF:

0.209

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.292

Gnomad OTH

AF:

0.305

GnomAD3 exomes

AF:

0.293

AC:

73589

AN:

251238

Hom.:

11300

AF XY:

0.297

AC XY:

40344

AN XY:

135784

show subpopulations

Gnomad AFR exome

AF:

0.316

Gnomad AMR exome

AF:

0.219

Gnomad ASJ exome

AF:

0.377

Gnomad EAS exome

AF:

0.376

Gnomad SAS exome

AF:

0.354

Gnomad FIN exome

AF:

0.210

Gnomad NFE exome

AF:

0.290

Gnomad OTH exome

AF:

0.305

GnomAD4 exome

AF:

0.294

AC:

429816

AN:

1459742

Hom.:

64570

Cov.:

AF XY:

0.297

AC XY:

215385

AN XY:

726278

show subpopulations

Gnomad4 AFR exome

AF:

0.321

Gnomad4 AMR exome

AF:

0.220

Gnomad4 ASJ exome

AF:

0.377

Gnomad4 EAS exome

AF:

0.370

Gnomad4 SAS exome

AF:

0.352

Gnomad4 FIN exome

AF:

0.216

Gnomad4 NFE exome

AF:

0.290

Gnomad4 OTH exome

AF:

0.309

GnomAD4 genome

AF:

0.295

AC:

44816

AN:

152144

Hom.:

6797

Cov.:

AF XY:

0.290

AC XY:

21592

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.313

Gnomad4 AMR

AF:

0.243

Gnomad4 ASJ

AF:

0.377

Gnomad4 EAS

AF:

0.381

Gnomad4 SAS

AF:

0.342

Gnomad4 FIN

AF:

0.209

Gnomad4 NFE

AF:

0.292

Gnomad4 OTH

AF:

0.304

Alfa

AF:

0.301

Hom.:

17236

Bravo

AF:

0.296

TwinsUK

AF:

0.281

AC:

1043

ALSPAC

AF:

0.287

AC:

1107

ESP6500AA

AF:

0.315

AC:

1386

ESP6500EA

AF:

0.290

AC:

2497

ExAC

AF:

0.296

AC:

35945

Asia WGS

AF:

0.357

AC:

1242

AN:

3478

EpiCase

AF:

0.301

EpiControl

AF:

0.298

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 18, 2020	This variant is associated with the following publications: (PMID: 31413141) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.88

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.0010

DANN

Benign

0.12

DEOGEN2

Benign

0.00076

.;T

Eigen

Benign

-2.7

Eigen_PC

Benign

-2.7

FATHMM_MKL

Benign

0.0012

LIST_S2

Benign

0.12

T;T

MetaRNN

Benign

0.0071

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.88

.;N

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.23

PROVEAN

Benign

0.23

.;N

REVEL

Benign

0.0060

Sift

Benign

0.84

.;T

Sift4G

Benign

0.63

.;T

Polyphen

0.0

.;B

Vest4

0.019

MPC

0.077

ClinPred

0.00041

GERP RS

-5.8

Varity_R

0.033

gMVP

0.078

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