11-60335034-G-T

Variant names:

• chr11-60335034-G-T
• rs2304933
• NM_139249.4:c.139G>T

Variant summary

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

The NM_139249.4(MS4A6E):​c.139G>T​(p.Val47Phe) 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 1,613,452 control chromosomes in the GnomAD database, including 89,900 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 (8395 hom., cov: 31)
  • Exomes 𝑓: 0.33 (81505 hom.)
• Consequence: MS4A6E NM_139249.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164
• Publications: 34 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=1.3646483E-4).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MS4A6E	NM_139249.4	c.139G>T	p.Val47Phe	missense_variant	Exon 2 of 5	ENST00000684409.1	NP_640342.1
MS4A6E	NR_170614.1	n.307G>T		non_coding_transcript_exon_variant	Exon 2 of 6
MS4A6E	NR_170615.1	n.307G>T		non_coding_transcript_exon_variant	Exon 2 of 5
MS4A6E	NR_170616.1	n.307G>T		non_coding_transcript_exon_variant	Exon 2 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MS4A6E	ENST00000684409.1	c.139G>T	p.Val47Phe	missense_variant	Exon 2 of 5		NM_139249.4	ENSP00000507799.1
MS4A6E	ENST00000300182.8	c.139G>T	p.Val47Phe	missense_variant	Exon 1 of 4	1		ENSP00000300182.4
MS4A6E	ENST00000530509.1	n.58G>T		non_coding_transcript_exon_variant	Exon 1 of 4	3		ENSP00000436675.1
MS4A6E	ENST00000532756.1	n.64G>T		non_coding_transcript_exon_variant	Exon 1 of 5	4		ENSP00000432963.1

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48458 AN: 151798 Hom.: 8373 Cov.: 31

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.292

GnomAD2 exomes AF: 0.324 AC: 81431 AN: 251242 AF XY: 0.315

Gnomad AFR exome AF: 0.249

Gnomad AMR exome AF: 0.385

Gnomad ASJ exome AF: 0.248

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: 0.327 AC: 477543 AN: 1461536 Hom.: 81505 Cov.: 38 AF XY: 0.321 AC XY: 233442 AN XY: 727070

African (AFR) AF: 0.248 AC: 8301 AN: 33474

American (AMR) AF: 0.377 AC: 16865 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 6600 AN: 26126

East Asian (EAS) AF: 0.298 AC: 11840 AN: 39696

South Asian (SAS) AF: 0.149 AC: 12864 AN: 86242

European-Finnish (FIN) AF: 0.544 AC: 29064 AN: 53406

Middle Eastern (MID) AF: 0.191 AC: 1104 AN: 5768

European-Non Finnish (NFE) AF: 0.335 AC: 372600 AN: 1111740

Other (OTH) AF: 0.303 AC: 18305 AN: 60388

GnomAD4 genome AF: 0.319 AC: 48523 AN: 151916 Hom.: 8395 Cov.: 31 AF XY: 0.327 AC XY: 24295 AN XY: 74238

African (AFR) AF: 0.250 AC: 10355 AN: 41432

American (AMR) AF: 0.362 AC: 5525 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 934 AN: 3468

East Asian (EAS) AF: 0.264 AC: 1364 AN: 5164

South Asian (SAS) AF: 0.150 AC: 720 AN: 4816

European-Finnish (FIN) AF: 0.570 AC: 5983 AN: 10504

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

European-Non Finnish (NFE) AF: 0.334 AC: 22712 AN: 67954

Other (OTH) AF: 0.295 AC: 622 AN: 2108

Alfa AF: 0.310 Hom.: 25576

Bravo AF: 0.304

TwinsUK AF: 0.345 AC: 1281

ALSPAC AF: 0.330 AC: 1273

ESP6500AA AF: 0.258 AC: 1137

ESP6500EA AF: 0.336 AC: 2890

ExAC AF: 0.318 AC: 38662

Asia WGS AF: 0.223 AC: 776 AN: 3478

EpiCase AF: 0.302

EpiControl AF: 0.303

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	8.4
DANN	Benign	0.96
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.60	T
MetaRNN	Benign	0.00014	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.16
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.044
Sift	Benign	0.044	D
Sift4G	Benign	0.098	T
Polyphen		1.0	D
Vest4		0.11
MPC		0.039
ClinPred		0.035	T
GERP RS		2.2
PromoterAI		-0.036	Neutral
Varity_R		0.14
gMVP		0.54
Mutation Taster		=92/8	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: rs2304933; hg19: chr11-60102507; COSMIC: COSV55728153;