rs17155019

Positions:

• chr11-60462204-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_152866.3(MS4A1):​c.-171C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00846 in 753,748 control chromosomes in the GnomAD database, including 269 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (77 hom., cov: 32)
  • Exomes 𝑓: 0.0078 (192 hom.)
• Consequence: MS4A1 NM_152866.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.130

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-60462204-C-T is Benign according to our data. Variant chr11-60462204-C-T is described in ClinVar as [Benign]. Clinvar id is 1229170.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MS4A1	NM_152866.3	c.-171C>T		5_prime_UTR_variant	3/8	ENST00000345732.9
MS4A1	NM_152867.2	c.-171C>T		5_prime_UTR_variant	2/7
MS4A1	NM_021950.4	c.-16-155C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MS4A1	ENST00000345732.9	c.-171C>T		5_prime_UTR_variant	3/8	1	NM_152866.3	P1

Frequencies

GnomAD3 genomes AF: 0.0109 AC: 1654 AN: 152130 Hom.: 77 Cov.: 32

Gnomad AFR AF: 0.00174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0864

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0354

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000676

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.0202 AC: 2862 AN: 141792 Hom.: 121 AF XY: 0.0164 AC XY: 1258 AN XY: 76586

Gnomad AFR exome AF: 0.000571

Gnomad AMR exome AF: 0.0904

Gnomad ASJ exome AF: 0.000119

Gnomad EAS exome AF: 0.0430

Gnomad SAS exome AF: 0.00236

Gnomad FIN exome AF: 0.000319

Gnomad NFE exome AF: 0.000471

Gnomad OTH exome AF: 0.0154

GnomAD4 exome AF: 0.00785 AC: 4721 AN: 601500 Hom.: 192 Cov.: 8 AF XY: 0.00669 AC XY: 2156 AN XY: 322240

Gnomad4 AFR exome AF: 0.00114

Gnomad4 AMR exome AF: 0.0929

Gnomad4 ASJ exome AF: 0.0000501

Gnomad4 EAS exome AF: 0.0270

Gnomad4 SAS exome AF: 0.00221

Gnomad4 FIN exome AF: 0.000150

Gnomad4 NFE exome AF: 0.000645

Gnomad4 OTH exome AF: 0.00927

GnomAD4 genome AF: 0.0109 AC: 1659 AN: 152248 Hom.: 77 Cov.: 32 AF XY: 0.0129 AC XY: 964 AN XY: 74440

Gnomad4 AFR AF: 0.00173

Gnomad4 AMR AF: 0.0866

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0356

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.000676

Gnomad4 OTH AF: 0.00994

Alfa AF: 0.00576 Hom.: 36

Bravo AF: 0.0161

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.9
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs17155019; hg19: chr11-60229677;