rs3802954

Positions:

• chr11-60470665-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MS4A1	NM_152866.3	c.*2197T>C		3_prime_UTR_variant	8/8	ENST00000345732.9
MS4A1	NM_021950.4	c.*2197T>C		3_prime_UTR_variant	7/7
MS4A1	NM_152867.2	c.*2197T>C		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MS4A1	ENST00000345732.9	c.*2197T>C		3_prime_UTR_variant	8/8	1	NM_152866.3	P1
MS4A1	ENST00000389939.2	c.*2197T>C		3_prime_UTR_variant	6/6	1		P1
MS4A1	ENST00000534668.6	c.*2197T>C		3_prime_UTR_variant	7/7	2		P1

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

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

Gnomad4 AFR AF: 0.0332

Gnomad4 AMR AF: 0.0405

Gnomad4 ASJ AF: 0.0467

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.0337

Gnomad4 NFE AF: 0.0784

Gnomad4 OTH AF: 0.0527

Alfa AF: 0.0748 Hom.: 416

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs3802954; hg19: chr11-60238138;