chr11-60071148-T-G

Position:

• chr11-60071148-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The 11-60071148-T-G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,136 control chromosomes in the GnomAD database, including 5,897 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 0.27 (5894 hom., cov: 32)
  • Exomes 𝑓: 0.16 (3 hom.)
• Consequence: MS4A3 NM_006138.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.676

Genes affected

MS4A3 (HGNC:7317): (membrane spanning 4-domains A3) This gene encodes a member of the membrane-spanning 4A gene family. Members of this protein family are characterized by common structural features and similar intron/exon splice boundaries and display unique expression patterns among hematopoietic cells and nonlymphoid tissues. This family member likely plays a role in signal transduction and may function as a subunit associated with receptor complexes. The gene encoding this protein is localized to 11q12, among a cluster of related family members. Alternative splicing may result in multiple transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MS4A3	NM_006138.5			downstream_gene_variant		ENST00000278865.8
MS4A3	NM_001031666.2			downstream_gene_variant
MS4A3	NM_001031809.2			downstream_gene_variant
MS4A3	XM_011545363.4			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MS4A3	ENST00000278865.8			downstream_gene_variant		1	NM_006138.5	P1
MS4A3	ENST00000358152.6			downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41533 AN: 151890 Hom.: 5893 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.287

GnomAD4 exome AF: 0.156 AC: 20 AN: 128 Hom.: 3 Cov.: 0 AF XY: 0.204 AC XY: 11 AN XY: 54

Gnomad4 FIN exome AF: 0.164

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.273 AC: 41561 AN: 152008 Hom.: 5894 Cov.: 32 AF XY: 0.274 AC XY: 20385 AN XY: 74288

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.291

Alfa AF: 0.296 Hom.: 3200

Bravo AF: 0.269

Asia WGS AF: 0.355 AC: 1233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.6
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs474951; hg19: chr11-59838621;