11-60232853-C-T

Variant names:

• chr11-60232853-C-T
• rs668134
• NM_001393391.1:c.-16-2782G>A

Variant summary

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

The NM_001393391.1(MS4A4E):​c.-16-2782G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.913 in 152,148 control chromosomes in the GnomAD database, including 63,558 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 0.91 (63558 hom., cov: 31)
• Consequence: MS4A4E NM_001393391.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393391.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A4E	NM_001393391.1	MANE Select	c.-16-2782G>A		intron	N/A	NP_001380320.1
	MS4A4E	NM_001351235.2		c.-89-2782G>A		intron	N/A	NP_001338164.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A4E	ENST00000651255.1	MANE Select	c.-16-2782G>A		intron	N/A	ENSP00000499123.1
	MS4A4A	ENST00000649552.2		c.59+46682C>T		intron	N/A	ENSP00000497952.2
	MS4A4A	ENST00000679553.1		c.59+46682C>T		intron	N/A	ENSP00000505712.1

Frequencies

GnomAD3 genomes AF: 0.913 AC: 138814 AN: 152030 Hom.: 63508 Cov.: 31

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.919

Gnomad AMR AF: 0.935

Gnomad ASJ AF: 0.857

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.919

Gnomad FIN AF: 0.977

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.916

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

GnomAD4 genome AF: 0.913 AC: 138916 AN: 152148 Hom.: 63558 Cov.: 31 AF XY: 0.915 AC XY: 68034 AN XY: 74380

African (AFR) AF: 0.854 AC: 35424 AN: 41486

American (AMR) AF: 0.935 AC: 14301 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.857 AC: 2974 AN: 3470

East Asian (EAS) AF: 0.853 AC: 4399 AN: 5160

South Asian (SAS) AF: 0.919 AC: 4430 AN: 4818

European-Finnish (FIN) AF: 0.977 AC: 10371 AN: 10618

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.941 AC: 63979 AN: 67990

Other (OTH) AF: 0.918 AC: 1937 AN: 2110

Alfa AF: 0.926 Hom.: 212338

Bravo AF: 0.906

Asia WGS AF: 0.879 AC: 3055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.2
DANN	Benign	0.26
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs668134; hg19: chr11-60000326;