Variant chr11-60339904-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_139249.4(MS4A6E):c.393G>A(p.Glu131=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00785 in 1,613,870 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0057 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0081 ( 63 hom. )

Consequence

MS4A6E
NM_139249.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.755

Variant links:

Genes affected

MS4A6E (HGNC:14285): (membrane spanning 4-domains A6E) This gene encodes a member of the membrane-spanning 4A gene family. Members of this nascent protein family are characterized by common structural features and similar intron/exon splice boundaries and display unique expression patterns among hematopoietic cells and nonlymphoid tissues. The gene encoding this protein is localized to 11q12.3, among a cluster of family members. [provided by RefSeq, Jul 2008]

MS4A6E links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 11-60339904-G-A is Benign according to our data. Variant chr11-60339904-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1176282.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.755 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MS4A6E	NM_139249.4 linkuse as main transcript	c.393G>A	p.Glu131=	synonymous_variant	4/5	ENST00000684409.1
MS4A6E	NR_170614.1 linkuse as main transcript	n.561G>A		non_coding_transcript_exon_variant	4/6
MS4A6E	NR_170616.1 linkuse as main transcript	n.681G>A		non_coding_transcript_exon_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MS4A6E	ENST00000684409.1 linkuse as main transcript	c.393G>A	p.Glu131=	synonymous_variant	4/5		NM_139249.4	P1
MS4A6E	ENST00000300182.8 linkuse as main transcript	c.393G>A	p.Glu131=	synonymous_variant	3/4	1		P1
MS4A6E	ENST00000532756.1 linkuse as main transcript	c.318G>A	p.Glu106=	synonymous_variant, NMD_transcript_variant	3/5	4

Frequencies

GnomAD3 genomes

AF:

0.00574

AC:

873

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00864

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00103

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00889

Gnomad OTH

AF:

0.00909

GnomAD3 exomes

AF:

0.00603

AC:

1516

AN:

251404

Hom.:

AF XY:

0.00614

AC XY:

834

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.00221

Gnomad AMR exome

AF:

0.00708

Gnomad ASJ exome

AF:

0.0112

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00225

Gnomad FIN exome

AF:

0.000832

Gnomad NFE exome

AF:

0.00865

Gnomad OTH exome

AF:

0.00782

GnomAD4 exome

AF:

0.00807

AC:

11793

AN:

1461532

Hom.:

Cov.:

AF XY:

0.00796

AC XY:

5786

AN XY:

727090

show subpopulations

Gnomad4 AFR exome

AF:

0.00128

Gnomad4 AMR exome

AF:

0.00738

Gnomad4 ASJ exome

AF:

0.0122

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00201

Gnomad4 FIN exome

AF:

0.000881

Gnomad4 NFE exome

AF:

0.00939

Gnomad4 OTH exome

AF:

0.00676

GnomAD4 genome

AF:

0.00573

AC:

873

AN:

152338

Hom.:

Cov.:

AF XY:

0.00546

AC XY:

407

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00147

Gnomad4 AMR

AF:

0.00863

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00103

Gnomad4 NFE

AF:

0.00889

Gnomad4 OTH

AF:

0.00900

Alfa

AF:

0.00742

Hom.:

Bravo

AF:

0.00613

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00927

EpiControl

AF:

0.0105

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

1.5

DANN

Benign

0.26

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