11-60204322-G-T

Variant names:

• chr11-60204322-G-T
• rs670139
• NM_001393391.1:c.659+568C>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.659+568C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,940 control chromosomes in the GnomAD database, including 13,664 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 0.42 (13664 hom., cov: 32)
• Consequence: MS4A4E NM_001393391.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 77 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.408 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.659+568C>A		intron	N/A	NP_001380320.1	A0A494C1L8
	MS4A4E	NM_001351235.2		c.279-2443C>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.659+568C>A		intron	N/A	ENSP00000499123.1	A0A494C1L8
	MS4A4A	ENST00000649552.2		c.59+18151G>T		intron	N/A	ENSP00000497952.2	A0A3B3ITV6
	MS4A4A	ENST00000679553.1		c.59+18151G>T		intron	N/A	ENSP00000505712.1	A0A7P0T9I4

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63486 AN: 151822 Hom.: 13649 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.418 AC: 63531 AN: 151940 Hom.: 13664 Cov.: 32 AF XY: 0.422 AC XY: 31357 AN XY: 74246

African (AFR) AF: 0.410 AC: 17005 AN: 41428

American (AMR) AF: 0.417 AC: 6363 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1139 AN: 3470

East Asian (EAS) AF: 0.413 AC: 2132 AN: 5166

South Asian (SAS) AF: 0.245 AC: 1184 AN: 4826

European-Finnish (FIN) AF: 0.611 AC: 6439 AN: 10536

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.412 AC: 27998 AN: 67930

Other (OTH) AF: 0.376 AC: 795 AN: 2112

Alfa AF: 0.378 Hom.: 6094

Bravo AF: 0.403

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.6
DANN	Benign	0.45
PhyloP100		1.1
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: rs670139; hg19: chr11-59971795;