ENST00000649552.2:c.60-17709G>A

Variant names:

• chr11-60274516-G-A
• rs77406754
• ENST00000649552.2:c.60-17709G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000649552.2(MS4A4A):​c.60-17709G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0162 in 151,974 control chromosomes in the GnomAD database, including 14 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 0.016 (14 hom., cov: 32)
• Consequence: MS4A4A ENST00000649552.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760
• Publications: 2 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=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0162 (2459/151974) while in subpopulation NFE AF = 0.0255 (1731/67906). AF 95% confidence interval is 0.0245. There are 14 homozygotes in GnomAd4. There are 1114 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

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.60-17709G>A		intron_variant	Intron 2 of 7			ENSP00000497952.2
MS4A4A	ENST00000679553.1	c.60-17709G>A		intron_variant	Intron 1 of 6			ENSP00000505712.1
MS4A4A	ENST00000681288.1	c.60-17709G>A		intron_variant	Intron 2 of 7			ENSP00000505714.1

Frequencies

GnomAD3 genomes AF: 0.0162 AC: 2459 AN: 151856 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.00457

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0171

Gnomad ASJ AF: 0.0378

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.0101

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0255

Gnomad OTH AF: 0.0130

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

GnomAD4 genome AF: 0.0162 AC: 2459 AN: 151974 Hom.: 14 Cov.: 32 AF XY: 0.0150 AC XY: 1114 AN XY: 74284

African (AFR) AF: 0.00456 AC: 189 AN: 41490

American (AMR) AF: 0.0171 AC: 260 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.0378 AC: 131 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4812

European-Finnish (FIN) AF: 0.0101 AC: 107 AN: 10586

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0255 AC: 1731 AN: 67906

Other (OTH) AF: 0.0128 AC: 27 AN: 2106

Alfa AF: 0.0230 Hom.: 77

Bravo AF: 0.0167

Asia WGS AF: 0.00289 AC: 10 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.39
PhyloP100		-0.076

Splicing

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

Other links and lift over

dbSNP: rs77406754; hg19: chr11-60041989;