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GeneBe

11-60339904-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

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

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.97).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.755 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MS4A6ENM_139249.4 linkuse as main transcriptc.393G>A p.Glu131= synonymous_variant 4/5 ENST00000684409.1
MS4A6ENR_170614.1 linkuse as main transcriptn.561G>A non_coding_transcript_exon_variant 4/6
MS4A6ENR_170616.1 linkuse as main transcriptn.681G>A non_coding_transcript_exon_variant 5/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MS4A6EENST00000684409.1 linkuse as main transcriptc.393G>A p.Glu131= synonymous_variant 4/5 NM_139249.4 P1
MS4A6EENST00000300182.8 linkuse as main transcriptc.393G>A p.Glu131= synonymous_variant 3/41 P1
MS4A6EENST00000532756.1 linkuse as main transcriptc.318G>A p.Glu106= synonymous_variant, NMD_transcript_variant 3/54

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00574
AC:
873
AN:
152220
Hom.:
3
Cov.:
32
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.:
16
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.:
63
Cov.:
31
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00573
AC:
873
AN:
152338
Hom.:
3
Cov.:
32
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.:
3
Bravo
AF:
0.00613
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.00927
EpiControl
AF:
0.0105

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenApr 01, 2021- -

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.

Other links and lift over

dbSNP: rs146311025; hg19: chr11-60107377; COSMIC: COSV105891290; COSMIC: COSV105891290; API