chr11-60232853-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MS4A4E	NM_001393391.1	c.-16-2782G>A		intron_variant	Intron 1 of 8	ENST00000651255.1	NP_001380320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MS4A4E	ENST00000651255.1	c.-16-2782G>A		intron_variant	Intron 1 of 8		NM_001393391.1	ENSP00000499123.1

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

Gnomad4 AFR AF: 0.854

Gnomad4 AMR AF: 0.935

Gnomad4 ASJ AF: 0.857

Gnomad4 EAS AF: 0.853

Gnomad4 SAS AF: 0.919

Gnomad4 FIN AF: 0.977

Gnomad4 NFE AF: 0.941

Gnomad4 OTH AF: 0.918

Alfa AF: 0.930 Hom.: 131816

Bravo AF: 0.906

Asia WGS AF: 0.879 AC: 3055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.2
DANN	Benign	0.26

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs668134; hg19: chr11-60000326;