chr11-60464852-A-G

Position:

• chr11-60464852-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MS4A1	NM_152866.3	c.336+508A>G		intron_variant		ENST00000345732.9
MS4A1	NM_021950.4	c.336+508A>G		intron_variant
MS4A1	NM_152867.2	c.336+508A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MS4A1	ENST00000345732.9	c.336+508A>G		intron_variant		1	NM_152866.3	P1

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

Gnomad4 AFR AF: 0.559

Gnomad4 AMR AF: 0.645

Gnomad4 ASJ AF: 0.738

Gnomad4 EAS AF: 0.665

Gnomad4 SAS AF: 0.589

Gnomad4 FIN AF: 0.814

Gnomad4 NFE AF: 0.706

Gnomad4 OTH AF: 0.652

Alfa AF: 0.689 Hom.: 49355

Bravo AF: 0.644

Asia WGS AF: 0.630 AC: 2191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs4939364; hg19: chr11-60232325;