rs2081547

Variant names:

• chr11-60221957-C-T
• rs2081547
• NM_001393391.1:c.178+6637G>A

Variant summary

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

The NM_001393391.1(MS4A4E):​c.178+6637G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,034 control chromosomes in the GnomAD database, including 8,785 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (8785 hom., cov: 32)
• Consequence: MS4A4E NM_001393391.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145
• Publications: 13 publications found

Genes affected

MS4A4E (HGNC:14284): (membrane spanning 4-domains A4E) Most MS4A genes, including MS4A4E, encode proteins with at least 4 potential transmembrane domains and N- and C-terminal cytoplasmic domains encoded by distinct exons.[supplied by OMIM, Apr 2004]

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MS4A4E	NM_001393391.1	c.178+6637G>A		intron_variant	Intron 3 of 8	ENST00000651255.1	NP_001380320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MS4A4E	ENST00000651255.1	c.178+6637G>A		intron_variant	Intron 3 of 8		NM_001393391.1	ENSP00000499123.1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47371 AN: 151916 Hom.: 8786 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.367

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.312 AC: 47381 AN: 152034 Hom.: 8785 Cov.: 32 AF XY: 0.312 AC XY: 23170 AN XY: 74302

African (AFR) AF: 0.108 AC: 4498 AN: 41504

American (AMR) AF: 0.392 AC: 5994 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1334 AN: 3466

East Asian (EAS) AF: 0.326 AC: 1682 AN: 5158

South Asian (SAS) AF: 0.509 AC: 2451 AN: 4814

European-Finnish (FIN) AF: 0.270 AC: 2851 AN: 10570

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.402 AC: 27332 AN: 67922

Other (OTH) AF: 0.369 AC: 780 AN: 2112

Alfa AF: 0.340 Hom.: 1598

Bravo AF: 0.312

Asia WGS AF: 0.377 AC: 1310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.4
DANN	Benign	0.44
PhyloP100		0.14
Mutation Taster		=100/0	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: rs2081547; hg19: chr11-59989430;