chr11-60234100-T-C

Position:

• chr11-60234100-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MS4A4E	NM_001393391.1	c.-16-4029A>G		intron_variant		ENST00000651255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MS4A4E	ENST00000651255.1	c.-16-4029A>G		intron_variant			NM_001393391.1	P1

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

Gnomad4 AFR AF: 0.351

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.611

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.365

Alfa AF: 0.395 Hom.: 6714

Bravo AF: 0.384

Asia WGS AF: 0.327 AC: 1135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.9
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs676309; hg19: chr11-60001573;