rs600550

Variant names:

• chr11-60230193-C-T
• rs600550
• NM_001393391.1:c.-16-122G>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.-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
• Publications: 22 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393391.1. 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
	MS4A4E	NM_001393391.1	MANE Select	c.-16-122G>A		intron	N/A	NP_001380320.1
	MS4A4E	NM_001351235.2		c.-89-122G>A		intron	N/A	NP_001338164.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A4E	ENST00000651255.1	MANE Select	c.-16-122G>A		intron	N/A	ENSP00000499123.1
	MS4A4A	ENST00000649552.2		c.59+44022C>T		intron	N/A	ENSP00000497952.2
	MS4A4A	ENST00000679553.1		c.59+44022C>T		intron	N/A	ENSP00000505712.1

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

African (AFR) AF: 0.408 AC: 8257 AN: 20246

American (AMR) AF: 0.403 AC: 5740 AN: 14250

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 5159 AN: 16208

East Asian (EAS) AF: 0.405 AC: 12281 AN: 30328

South Asian (SAS) AF: 0.247 AC: 11308 AN: 45750

European-Finnish (FIN) AF: 0.581 AC: 18897 AN: 32524

Middle Eastern (MID) AF: 0.309 AC: 912 AN: 2956

European-Non Finnish (NFE) AF: 0.405 AC: 295760 AN: 730104

Other (OTH) AF: 0.384 AC: 15977 AN: 41564

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

African (AFR) AF: 0.410 AC: 16990 AN: 41398

American (AMR) AF: 0.416 AC: 6341 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1134 AN: 3472

East Asian (EAS) AF: 0.414 AC: 2135 AN: 5156

South Asian (SAS) AF: 0.253 AC: 1219 AN: 4818

European-Finnish (FIN) AF: 0.612 AC: 6442 AN: 10522

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27958 AN: 67942

Other (OTH) AF: 0.375 AC: 793 AN: 2112

Alfa AF: 0.405 Hom.: 47638

Bravo AF: 0.403

Asia WGS AF: 0.332 AC: 1153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.094
DANN	Benign	0.16
PhyloP100		-2.0
PromoterAI		-0.017	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

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