rs3802954

Variant names:

• chr11-60470665-T-C
• rs3802954
• NM_152866.3:c.*2197T>C

Variant summary

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

The NM_152866.3(MS4A1):​c.*2197T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0624 in 152,088 control chromosomes in the GnomAD database, including 371 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 0.062 (371 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: MS4A1 NM_152866.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.788
• Publications: 4 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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MS4A1	NM_152866.3	c.*2197T>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000345732.9	NP_690605.1
MS4A1	NM_021950.4	c.*2197T>C		3_prime_UTR_variant	Exon 7 of 7		NP_068769.2
MS4A1	NM_152867.2	c.*2197T>C		3_prime_UTR_variant	Exon 7 of 7		NP_690606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MS4A1	ENST00000345732.9	c.*2197T>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_152866.3	ENSP00000314620.7
MS4A1	ENST00000389939.2	c.*2197T>C		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000374589.2
MS4A1	ENST00000534668.6	c.*2197T>C		3_prime_UTR_variant	Exon 7 of 7	2		ENSP00000433277.1

Frequencies

GnomAD3 genomes AF: 0.0624 AC: 9481 AN: 151968 Hom.: 371 Cov.: 32

Gnomad AFR AF: 0.0332

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0407

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.0337

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0784

Gnomad OTH AF: 0.0533

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0624 AC: 9483 AN: 152088 Hom.: 371 Cov.: 32 AF XY: 0.0625 AC XY: 4644 AN XY: 74362

African (AFR) AF: 0.0332 AC: 1381 AN: 41566

American (AMR) AF: 0.0405 AC: 619 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0467 AC: 162 AN: 3466

East Asian (EAS) AF: 0.113 AC: 585 AN: 5180

South Asian (SAS) AF: 0.173 AC: 835 AN: 4820

European-Finnish (FIN) AF: 0.0337 AC: 358 AN: 10616

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0784 AC: 5319 AN: 67854

Other (OTH) AF: 0.0527 AC: 111 AN: 2106

Alfa AF: 0.0741 Hom.: 482

Bravo AF: 0.0589

Asia WGS AF: 0.143 AC: 496 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.8
DANN	Benign	0.85
PhyloP100		0.79
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: rs3802954; hg19: chr11-60238138;