chr11-60464852-A-G

Variant names:

• chr11-60464852-A-G
• rs4939364
• NM_152866.3:c.336+508A>G

Variant summary

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

The NM_152866.3(MS4A1):​c.336+508A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 152,070 control chromosomes in the GnomAD database, including 33,899 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 0.66 (33899 hom., cov: 32)
• Consequence: MS4A1 NM_152866.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101
• Publications: 10 publications found

Genes affected

MS4A1 (HGNC:7315): (membrane spanning 4-domains A1) This gene encodes a member of the membrane-spanning 4A gene family. Members of this nascent 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 gene encodes a B-lymphocyte surface molecule which plays a role in the development and differentiation of B-cells into plasma cells. This family member is localized to 11q12, among a cluster of family members. Alternative splicing of this gene results in two transcript variants which encode the same protein. [provided by RefSeq, Jul 2008]

MS4A1 Gene-Disease associations (from GenCC):

• common variable immunodeficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• immunodeficiency, common variable, 5

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152866.3. 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
	MS4A1	NM_152866.3	MANE Select	c.336+508A>G		intron	N/A	NP_690605.1
	MS4A1	NM_021950.4		c.336+508A>G		intron	N/A	NP_068769.2
	MS4A1	NM_152867.2		c.336+508A>G		intron	N/A	NP_690606.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A1	ENST00000345732.9	TSL:1 MANE Select	c.336+508A>G		intron	N/A	ENSP00000314620.7
	MS4A1	ENST00000389939.2	TSL:1	c.336+508A>G		intron	N/A	ENSP00000374589.2
	MS4A1	ENST00000532073.5	TSL:1	c.336+508A>G		intron	N/A	ENSP00000433519.1

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100543 AN: 151952 Hom.: 33873 Cov.: 32

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.706

Gnomad OTH AF: 0.650

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

GnomAD4 genome AF: 0.662 AC: 100625 AN: 152070 Hom.: 33899 Cov.: 32 AF XY: 0.665 AC XY: 49424 AN XY: 74352

African (AFR) AF: 0.559 AC: 23153 AN: 41452

American (AMR) AF: 0.645 AC: 9861 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 2561 AN: 3472

East Asian (EAS) AF: 0.665 AC: 3439 AN: 5172

South Asian (SAS) AF: 0.589 AC: 2832 AN: 4808

European-Finnish (FIN) AF: 0.814 AC: 8633 AN: 10600

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.706 AC: 47950 AN: 67964

Other (OTH) AF: 0.652 AC: 1377 AN: 2112

Alfa AF: 0.685 Hom.: 61461

Bravo AF: 0.644

Asia WGS AF: 0.630 AC: 2191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.43
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4939364; hg19: chr11-60232325;