11-60062205-G-C

Position:

• chr11-60062205-G-C

Variant summary

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

The NM_006138.5(MS4A3):​c.157-263G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 151,874 control chromosomes in the GnomAD database, including 29,871 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 0.62 (29871 hom., cov: 30)
• Consequence: MS4A3 NM_006138.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.112

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MS4A3	NM_006138.5	c.157-263G>C		intron_variant		ENST00000278865.8	NP_006129.4
MS4A3	NM_001031809.2	c.156+889G>C		intron_variant			NP_001026979.1
MS4A3	NM_001031666.2	c.-75-2057G>C		intron_variant			NP_001026836.1
MS4A3	XM_011545363.4	c.-24-263G>C		intron_variant			XP_011543665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MS4A3	ENST00000278865.8	c.157-263G>C		intron_variant		1	NM_006138.5	ENSP00000278865.3

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94743 AN: 151756 Hom.: 29832 Cov.: 30

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.625 AC: 94849 AN: 151874 Hom.: 29871 Cov.: 30 AF XY: 0.632 AC XY: 46925 AN XY: 74240

Gnomad4 AFR AF: 0.597

Gnomad4 AMR AF: 0.694

Gnomad4 ASJ AF: 0.552

Gnomad4 EAS AF: 0.816

Gnomad4 SAS AF: 0.681

Gnomad4 FIN AF: 0.673

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.623

Alfa AF: 0.494 Hom.: 1343

Bravo AF: 0.626

Asia WGS AF: 0.744 AC: 2584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.6
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs507035; hg19: chr11-59829678;