11-60266956-C-T

Variant names:

• chr11-60266956-C-T
• rs4938933
• ENST00000649552.2:c.60-25269C>T

Variant summary

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

The ENST00000649552.2(MS4A4A):​c.60-25269C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 151,862 control chromosomes in the GnomAD database, including 30,468 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 0.63 (30468 hom., cov: 30)
• Consequence: MS4A4A ENST00000649552.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870
• Publications: 79 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MS4A4A	ENST00000649552.2	c.60-25269C>T		intron_variant	Intron 2 of 7			ENSP00000497952.2
MS4A4A	ENST00000679553.1	c.60-25269C>T		intron_variant	Intron 1 of 6			ENSP00000505712.1
MS4A4A	ENST00000681288.1	c.60-25269C>T		intron_variant	Intron 2 of 7			ENSP00000505714.1

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95684 AN: 151744 Hom.: 30456 Cov.: 30

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.733

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.592

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

GnomAD4 genome AF: 0.630 AC: 95738 AN: 151862 Hom.: 30468 Cov.: 30 AF XY: 0.634 AC XY: 47036 AN XY: 74220

African (AFR) AF: 0.688 AC: 28497 AN: 41410

American (AMR) AF: 0.584 AC: 8905 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2126 AN: 3466

East Asian (EAS) AF: 0.705 AC: 3624 AN: 5140

South Asian (SAS) AF: 0.495 AC: 2375 AN: 4800

European-Finnish (FIN) AF: 0.733 AC: 7736 AN: 10552

Middle Eastern (MID) AF: 0.521 AC: 152 AN: 292

European-Non Finnish (NFE) AF: 0.596 AC: 40485 AN: 67934

Other (OTH) AF: 0.591 AC: 1241 AN: 2100

Alfa AF: 0.604 Hom.: 111608

Bravo AF: 0.622

Asia WGS AF: 0.621 AC: 2159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.6
DANN	Benign	0.48
PhyloP100		0.087

Splicing

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

Other links and lift over

dbSNP: rs4938933; hg19: chr11-60034429;