NM_001393391.1:c.-16-4029A>G

Variant names:

• chr11-60234100-T-C
• rs676309
• NM_001393391.1:c.-16-4029A>G

Variant summary

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

The NM_001393391.1(MS4A4E):​c.-16-4029A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 151,986 control chromosomes in the GnomAD database, including 12,652 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 0.40 (12652 hom., cov: 32)
• Consequence: MS4A4E NM_001393391.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.283
• Publications: 19 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.407 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.-16-4029A>G		intron	N/A	NP_001380320.1
	MS4A4E	NM_001351235.2		c.-89-4029A>G		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.-16-4029A>G		intron	N/A	ENSP00000499123.1
	MS4A4A	ENST00000649552.2		c.59+47929T>C		intron	N/A	ENSP00000497952.2
	MS4A4A	ENST00000679553.1		c.59+47929T>C		intron	N/A	ENSP00000505712.1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60862 AN: 151868 Hom.: 12641 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.401 AC: 60894 AN: 151986 Hom.: 12652 Cov.: 32 AF XY: 0.407 AC XY: 30210 AN XY: 74278

African (AFR) AF: 0.351 AC: 14541 AN: 41446

American (AMR) AF: 0.409 AC: 6250 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1133 AN: 3466

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

South Asian (SAS) AF: 0.253 AC: 1218 AN: 4818

European-Finnish (FIN) AF: 0.611 AC: 6438 AN: 10544

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27940 AN: 67944

Other (OTH) AF: 0.365 AC: 772 AN: 2114

Alfa AF: 0.395 Hom.: 7409

Bravo AF: 0.384

Asia WGS AF: 0.327 AC: 1135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.9
DANN	Benign	0.60
PhyloP100		0.28
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: rs676309; hg19: chr11-60001573;