rs2868121

Positions:

• chr11-60332956-G-A
• chr11-60332956-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139249.4(MS4A6E):​c.-14-1926G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,080 control chromosomes in the GnomAD database, including 10,274 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 0.36 (10274 hom., cov: 33)
• Consequence: MS4A6E NM_139249.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.916

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MS4A6E	NM_139249.4	c.-14-1926G>A		intron_variant		ENST00000684409.1
MS4A6E	NR_170614.1	n.155-1926G>A		intron_variant, non_coding_transcript_variant
MS4A6E	NR_170615.1	n.155-1926G>A		intron_variant, non_coding_transcript_variant
MS4A6E	NR_170616.1	n.155-1926G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MS4A6E	ENST00000684409.1	c.-14-1926G>A		intron_variant			NM_139249.4	P1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54387 AN: 151962 Hom.: 10252 Cov.: 33

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.358 AC: 54453 AN: 152080 Hom.: 10274 Cov.: 33 AF XY: 0.366 AC XY: 27223 AN XY: 74316

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.396

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.408

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.583

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.338

Alfa AF: 0.352 Hom.: 1552

Bravo AF: 0.345

Asia WGS AF: 0.293 AC: 1020 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.28
DANN	Benign	0.62

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2868121; hg19: chr11-60100429;