11-60207605-C-T

Variant summary

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

The NM_001393391.1(MS4A4E):c.483+988G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 152,006 control chromosomes in the GnomAD database, including 9,442 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 (9442 hom., cov: 31)
• Consequence: MS4A4E NM_001393391.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.253

Genes affected

MS4A4E (HGNC:14284): (membrane spanning 4-domains A4E) Most MS4A genes, including MS4A4E, encode proteins with at least 4 potential transmembrane domains and N- and C-terminal cytoplasmic domains encoded by distinct exons.[supplied by OMIM, Apr 2004]

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MS4A4E	NM_001393391.1	c.483+988G>A		intron_variant		ENST00000651255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MS4A4E	ENST00000651255.1	c.483+988G>A		intron_variant			NM_001393391.1	P1

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51260 AN: 151888 Hom.: 9439 Cov.: 31

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.337 AC: 51279 AN: 152006 Hom.: 9442 Cov.: 31 AF XY: 0.337 AC XY: 25025 AN XY: 74306

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.402

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.512

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.403

Gnomad4 OTH AF: 0.387

Alfa AF: 0.403 Hom.: 16712

Bravo AF: 0.341

Asia WGS AF: 0.391 AC: 1362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.3
Dann	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7929589; hg19: chr11-59975078;