11-60207605-C-T

Variant names:

• chr11-60207605-C-T
• rs7929589
• NM_001393391.1:c.483+988G>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.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
• Publications: 22 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.495 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A4E	NM_001393391.1	MANE Select	c.483+988G>A		intron	N/A	NP_001380320.1	A0A494C1L8
	MS4A4E	NM_001351235.2		c.279-5726G>A		intron	N/A	NP_001338164.1	B4DT89

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A4E	ENST00000651255.1	MANE Select	c.483+988G>A		intron	N/A	ENSP00000499123.1	A0A494C1L8
	MS4A4A	ENST00000649552.2		c.59+21434C>T		intron	N/A	ENSP00000497952.2	A0A3B3ITV6
	MS4A4A	ENST00000679553.1		c.59+21434C>T		intron	N/A	ENSP00000505712.1	A0A7P0T9I4

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

African (AFR) AF: 0.195 AC: 8099 AN: 41460

American (AMR) AF: 0.402 AC: 6149 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1343 AN: 3472

East Asian (EAS) AF: 0.329 AC: 1703 AN: 5174

South Asian (SAS) AF: 0.512 AC: 2465 AN: 4812

European-Finnish (FIN) AF: 0.271 AC: 2861 AN: 10564

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.403 AC: 27377 AN: 67928

Other (OTH) AF: 0.387 AC: 818 AN: 2112

Alfa AF: 0.395 Hom.: 20487

Bravo AF: 0.341

Asia WGS AF: 0.391 AC: 1362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.49
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7929589; hg19: chr11-59975078;