11-60469937-C-T

Variant names:

• chr11-60469937-C-T
• rs3802957
• NM_152866.3:c.*1469C>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.*1469C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0502 in 151,912 control chromosomes in the GnomAD database, including 268 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 0.050 (268 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: MS4A1 NM_152866.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482
• Publications: 7 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MS4A1	NM_152866.3	c.*1469C>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000345732.9	NP_690605.1
MS4A1	NM_021950.4	c.*1469C>T		3_prime_UTR_variant	Exon 7 of 7		NP_068769.2
MS4A1	NM_152867.2	c.*1469C>T		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.*1469C>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_152866.3	ENSP00000314620.7

Frequencies

GnomAD3 genomes AF: 0.0502 AC: 7618 AN: 151794 Hom.: 268 Cov.: 32

Gnomad AFR AF: 0.0470

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0329

Gnomad ASJ AF: 0.0520

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.0814

Gnomad FIN AF: 0.0733

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0397

Gnomad OTH AF: 0.0495

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: 0.0502 AC: 7628 AN: 151912 Hom.: 268 Cov.: 32 AF XY: 0.0533 AC XY: 3955 AN XY: 74254

African (AFR) AF: 0.0471 AC: 1954 AN: 41470

American (AMR) AF: 0.0330 AC: 503 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0520 AC: 180 AN: 3464

East Asian (EAS) AF: 0.194 AC: 1002 AN: 5164

South Asian (SAS) AF: 0.0812 AC: 390 AN: 4802

European-Finnish (FIN) AF: 0.0733 AC: 774 AN: 10564

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0397 AC: 2697 AN: 67886

Other (OTH) AF: 0.0490 AC: 103 AN: 2104

Alfa AF: 0.0424 Hom.: 254

Bravo AF: 0.0482

Asia WGS AF: 0.104 AC: 361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.7
DANN	Benign	0.27
PhyloP100		-0.48
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: rs3802957; hg19: chr11-60237410;