11-60334923-A-G

Variant names:

• chr11-60334923-A-G
• rs2304934
• NM_139249.4:c.28A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139249.4(MS4A6E):​c.28A>G​(p.Thr10Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 1,610,398 control chromosomes in the GnomAD database, including 89,867 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (8424 hom., cov: 32)
  • Exomes 𝑓: 0.33 (81443 hom.)
• Consequence: MS4A6E NM_139249.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111
• Publications: 26 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.1028645E-5).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139249.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A6E	NM_139249.4	MANE Select	c.28A>G	p.Thr10Ala	missense	Exon 2 of 5	NP_640342.1
	MS4A6E	NR_170614.1		n.196A>G		non_coding_transcript_exon	Exon 2 of 6
	MS4A6E	NR_170615.1		n.196A>G		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A6E	ENST00000684409.1	MANE Select	c.28A>G	p.Thr10Ala	missense	Exon 2 of 5	ENSP00000507799.1
	MS4A6E	ENST00000300182.8	TSL:1	c.28A>G	p.Thr10Ala	missense	Exon 1 of 4	ENSP00000300182.4
	MS4A6E	ENST00000530509.1	TSL:3	n.-54A>G		upstream_gene	N/A	ENSP00000436675.1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48581 AN: 151924 Hom.: 8402 Cov.: 32

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.292

GnomAD2 exomes AF: 0.324 AC: 81533 AN: 251450 AF XY: 0.315

Gnomad AFR exome AF: 0.250

Gnomad AMR exome AF: 0.385

Gnomad ASJ exome AF: 0.247

Gnomad EAS exome AF: 0.269

Gnomad FIN exome AF: 0.559

Gnomad NFE exome AF: 0.337

Gnomad OTH exome AF: 0.306

GnomAD4 exome AF: 0.326 AC: 475808 AN: 1458356 Hom.: 81443 Cov.: 37 AF XY: 0.321 AC XY: 232709 AN XY: 725756

African (AFR) AF: 0.249 AC: 8318 AN: 33418

American (AMR) AF: 0.378 AC: 16892 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 6592 AN: 26120

East Asian (EAS) AF: 0.298 AC: 11845 AN: 39684

South Asian (SAS) AF: 0.149 AC: 12846 AN: 86202

European-Finnish (FIN) AF: 0.544 AC: 29059 AN: 53412

Middle Eastern (MID) AF: 0.192 AC: 1105 AN: 5766

European-Non Finnish (NFE) AF: 0.335 AC: 370895 AN: 1108748

Other (OTH) AF: 0.303 AC: 18256 AN: 60288

GnomAD4 genome AF: 0.320 AC: 48646 AN: 152042 Hom.: 8424 Cov.: 32 AF XY: 0.328 AC XY: 24364 AN XY: 74308

African (AFR) AF: 0.252 AC: 10432 AN: 41464

American (AMR) AF: 0.362 AC: 5536 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 935 AN: 3472

East Asian (EAS) AF: 0.265 AC: 1368 AN: 5172

South Asian (SAS) AF: 0.150 AC: 725 AN: 4824

European-Finnish (FIN) AF: 0.571 AC: 6011 AN: 10532

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22706 AN: 67984

Other (OTH) AF: 0.295 AC: 623 AN: 2114

Alfa AF: 0.320 Hom.: 18981

Bravo AF: 0.304

TwinsUK AF: 0.343 AC: 1272

ALSPAC AF: 0.328 AC: 1264

ESP6500AA AF: 0.260 AC: 1144

ESP6500EA AF: 0.336 AC: 2888

ExAC AF: 0.318 AC: 38654

Asia WGS AF: 0.223 AC: 775 AN: 3478

EpiCase AF: 0.302

EpiControl AF: 0.302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.99
DANN	Benign	0.96
DEOGEN2	Benign	0.037	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0044	N
LIST_S2	Benign	0.56	T
MetaRNN	Benign	0.000051	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.11
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.022
Sift	Benign	0.086	T
Sift4G	Uncertain	0.023	D
Polyphen		0.11	B
Vest4		0.0080
MPC		0.052
ClinPred		0.010	T
GERP RS		-2.8
PromoterAI		0.056	Neutral
Varity_R		0.051
gMVP		0.24
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2304934; hg19: chr11-60102396; COSMIC: COSV55726789; COSMIC: COSV55726789;