rs1026250

Variant names:

• chr11-60286718-G-C
• rs1026250
• NM_148975.3:c.42-5507G>C

Variant summary

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

The NM_148975.3(MS4A4A):​c.42-5507G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,106 control chromosomes in the GnomAD database, including 3,111 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 0.18 (3111 hom., cov: 32)
• Consequence: MS4A4A NM_148975.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.932
• Publications: 6 publications found

Genes affected

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MS4A4A	NM_148975.3	c.42-5507G>C		intron_variant	Intron 1 of 6	ENST00000337908.5	NP_683876.1
MS4A4A	NM_024021.4	c.-17+3979G>C		intron_variant	Intron 2 of 7		NP_076926.2
MS4A4A	NM_001243266.2	c.42-5507G>C		intron_variant	Intron 1 of 5		NP_001230195.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MS4A4A	ENST00000337908.5	c.42-5507G>C		intron_variant	Intron 1 of 6	1	NM_148975.3	ENSP00000338648.4

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26801 AN: 151988 Hom.: 3105 Cov.: 32

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.0517

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.176 AC: 26838 AN: 152106 Hom.: 3111 Cov.: 32 AF XY: 0.172 AC XY: 12754 AN XY: 74358

African (AFR) AF: 0.326 AC: 13521 AN: 41458

American (AMR) AF: 0.113 AC: 1721 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 721 AN: 3470

East Asian (EAS) AF: 0.125 AC: 648 AN: 5174

South Asian (SAS) AF: 0.166 AC: 804 AN: 4830

European-Finnish (FIN) AF: 0.0517 AC: 548 AN: 10594

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8265 AN: 67990

Other (OTH) AF: 0.163 AC: 344 AN: 2114

Alfa AF: 0.150 Hom.: 317

Bravo AF: 0.186

Asia WGS AF: 0.151 AC: 524 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	0.57
DANN	Benign	0.13
PhyloP100		-0.93
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: rs1026250; hg19: chr11-60054191;