11-60254475-G-A

Position:

• chr11-60254475-G-A

Variant summary

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

The ENST00000649552.2(MS4A4A):​c.60-37750G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,010 control chromosomes in the GnomAD database, including 7,355 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 0.28 (7355 hom., cov: 32)
• Consequence: MS4A4A ENST00000649552.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.328

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MS4A4A	ENST00000649552.2	c.60-37750G>A		intron_variant				ENSP00000497952	A2
MS4A4A	ENST00000679385.1	c.-24-42722G>A		intron_variant				ENSP00000506313
MS4A4A	ENST00000679553.1	c.60-37750G>A		intron_variant				ENSP00000505712	A2

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42892 AN: 151892 Hom.: 7354 Cov.: 32

Gnomad AFR AF: 0.0907

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.282 AC: 42902 AN: 152010 Hom.: 7355 Cov.: 32 AF XY: 0.282 AC XY: 20916 AN XY: 74300

Gnomad4 AFR AF: 0.0906

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.331

Alfa AF: 0.367 Hom.: 10079

Bravo AF: 0.281

Asia WGS AF: 0.287 AC: 998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.5
DANN	Benign	0.31

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1582763; hg19: chr11-60021948;