rs77406754

Positions:

• chr11-60274516-G-A

Variant summary

Our verdict is Benign. Variant got -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

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).
• 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

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.60-17709G>A		intron_variant				ENSP00000497952	A2
MS4A4A	ENST00000679385.1	c.-24-22681G>A		intron_variant				ENSP00000506313
MS4A4A	ENST00000679553.1	c.60-17709G>A		intron_variant				ENSP00000505712	A2

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

Gnomad4 AFR AF: 0.00456

Gnomad4 AMR AF: 0.0171

Gnomad4 ASJ AF: 0.0378

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.0101

Gnomad4 NFE AF: 0.0255

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.0225 Hom.: 10

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs77406754; hg19: chr11-60041989;