11-60062205-G-C

Variant names:

• chr11-60062205-G-C
• rs507035
• NM_006138.5:c.157-263G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006138.5. 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
	MS4A3	NM_006138.5	MANE Select	c.157-263G>C		intron	N/A	NP_006129.4
	MS4A3	NM_001031809.2		c.156+889G>C		intron	N/A	NP_001026979.1
	MS4A3	NM_001031666.2		c.-75-2057G>C		intron	N/A	NP_001026836.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A3	ENST00000278865.8	TSL:1 MANE Select	c.157-263G>C		intron	N/A	ENSP00000278865.3
	MS4A3	ENST00000358152.6	TSL:5	c.156+889G>C		intron	N/A	ENSP00000350872.2
	MS4A3	ENST00000395032.6	TSL:2	c.-75-2057G>C		intron	N/A	ENSP00000378473.2

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

African (AFR) AF: 0.597 AC: 24674 AN: 41356

American (AMR) AF: 0.694 AC: 10591 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1915 AN: 3468

East Asian (EAS) AF: 0.816 AC: 4211 AN: 5160

South Asian (SAS) AF: 0.681 AC: 3284 AN: 4820

European-Finnish (FIN) AF: 0.673 AC: 7095 AN: 10538

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41087 AN: 67956

Other (OTH) AF: 0.623 AC: 1311 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.6
DANN	Benign	0.65
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs507035; hg19: chr11-59829678;