rs600550

Positions:

• chr11-60230193-C-T

Variant summary

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

The NM_001393391.1(MS4A4E):​c.-16-122G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,085,806 control chromosomes in the GnomAD database, including 91,068 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 0.42 (13662 hom., cov: 31)
  • Exomes 𝑓: 0.40 (77406 hom.)
• Consequence: MS4A4E NM_001393391.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MS4A4E	NM_001393391.1	c.-16-122G>A		intron_variant		ENST00000651255.1	NP_001380320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MS4A4E	ENST00000651255.1	c.-16-122G>A		intron_variant			NM_001393391.1	ENSP00000499123.1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63440 AN: 151758 Hom.: 13648 Cov.: 31

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.375

GnomAD4 exome AF: 0.401 AC: 374291 AN: 933930 Hom.: 77406 AF XY: 0.396 AC XY: 182916 AN XY: 461486

Gnomad4 AFR exome AF: 0.408

Gnomad4 AMR exome AF: 0.403

Gnomad4 ASJ exome AF: 0.318

Gnomad4 EAS exome AF: 0.405

Gnomad4 SAS exome AF: 0.247

Gnomad4 FIN exome AF: 0.581

Gnomad4 NFE exome AF: 0.405

Gnomad4 OTH exome AF: 0.384

GnomAD4 genome AF: 0.418 AC: 63485 AN: 151876 Hom.: 13662 Cov.: 31 AF XY: 0.422 AC XY: 31356 AN XY: 74218

Gnomad4 AFR AF: 0.410

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.375

Alfa AF: 0.399 Hom.: 20381

Bravo AF: 0.403

Asia WGS AF: 0.332 AC: 1153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.094
DANN	Benign	0.16

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs600550; hg19: chr11-59997666; COSMIC: COSV67519073;