11-60198822-T-C

Variant names:

• chr11-60198822-T-C
• rs2123314
• ENST00000649552.2:c.59+12651T>C

Variant summary

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

The ENST00000649552.2(MS4A4A):​c.59+12651T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 151,998 control chromosomes in the GnomAD database, including 9,264 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 0.34 (9264 hom., cov: 32)
• Consequence: MS4A4A ENST00000649552.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 12 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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.477 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.59+12651T>C		intron_variant	Intron 2 of 7			ENSP00000497952.2
MS4A4A	ENST00000679553.1	c.59+12651T>C		intron_variant	Intron 1 of 6			ENSP00000505712.1
MS4A4A	ENST00000681288.1	c.59+12651T>C		intron_variant	Intron 2 of 7			ENSP00000505714.1

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51545 AN: 151878 Hom.: 9260 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.339 AC: 51583 AN: 151998 Hom.: 9264 Cov.: 32 AF XY: 0.336 AC XY: 24960 AN XY: 74298

African (AFR) AF: 0.251 AC: 10416 AN: 41460

American (AMR) AF: 0.305 AC: 4656 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1337 AN: 3468

East Asian (EAS) AF: 0.218 AC: 1126 AN: 5176

South Asian (SAS) AF: 0.494 AC: 2379 AN: 4816

European-Finnish (FIN) AF: 0.278 AC: 2939 AN: 10558

Middle Eastern (MID) AF: 0.473 AC: 138 AN: 292

European-Non Finnish (NFE) AF: 0.403 AC: 27399 AN: 67916

Other (OTH) AF: 0.378 AC: 800 AN: 2114

Alfa AF: 0.346 Hom.: 1489

Bravo AF: 0.335

Asia WGS AF: 0.352 AC: 1223 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.52
DANN	Benign	0.28
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs2123314; hg19: chr11-59966295;