11-60463593-C-T

Variant names:

• chr11-60463593-C-T
• rs7126354
• NM_152866.3:c.279+472C>T

Variant summary

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

The NM_152866.3(MS4A1):​c.279+472C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 152,068 control chromosomes in the GnomAD database, including 31,295 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 0.64 (31295 hom., cov: 32)
• Consequence: MS4A1 NM_152866.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.631
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.688 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A1	NM_152866.3	MANE Select	c.279+472C>T		intron	N/A	NP_690605.1	P11836-1
	MS4A1	NM_021950.4		c.279+472C>T		intron	N/A	NP_068769.2
	MS4A1	NM_152867.2		c.279+472C>T		intron	N/A	NP_690606.1	P11836-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A1	ENST00000345732.9	TSL:1 MANE Select	c.279+472C>T		intron	N/A	ENSP00000314620.7	P11836-1
	MS4A1	ENST00000389939.2	TSL:1	c.279+472C>T		intron	N/A	ENSP00000374589.2	P11836-1
	MS4A1	ENST00000532073.5	TSL:1	c.279+472C>T		intron	N/A	ENSP00000433519.1	E9PKH8

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97248 AN: 151950 Hom.: 31264 Cov.: 32

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.653

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

GnomAD4 genome AF: 0.640 AC: 97332 AN: 152068 Hom.: 31295 Cov.: 32 AF XY: 0.637 AC XY: 47313 AN XY: 74328

African (AFR) AF: 0.688 AC: 28524 AN: 41476

American (AMR) AF: 0.700 AC: 10692 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 2114 AN: 3472

East Asian (EAS) AF: 0.627 AC: 3243 AN: 5172

South Asian (SAS) AF: 0.607 AC: 2918 AN: 4808

European-Finnish (FIN) AF: 0.537 AC: 5668 AN: 10556

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.618 AC: 42036 AN: 67988

Other (OTH) AF: 0.651 AC: 1371 AN: 2106

Alfa AF: 0.587 Hom.: 3211

Bravo AF: 0.655

Asia WGS AF: 0.636 AC: 2213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.75
PhyloP100		-0.63
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: rs7126354; hg19: chr11-60231066;