11-60462204-C-T

Variant names:

• chr11-60462204-C-T
• rs17155019
• NM_152866.3:c.-171C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.130
• Publications: 3 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 -20 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 VariationId is 1229170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0827 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152866.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A1	NM_152866.3	MANE Select	c.-171C>T		5_prime_UTR	Exon 3 of 8	NP_690605.1
	MS4A1	NM_152867.2		c.-171C>T		5_prime_UTR	Exon 2 of 7	NP_690606.1
	MS4A1	NM_021950.4		c.-16-155C>T		intron	N/A	NP_068769.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A1	ENST00000345732.9	TSL:1 MANE Select	c.-171C>T		5_prime_UTR	Exon 3 of 8	ENSP00000314620.7
	MS4A1	ENST00000389939.2	TSL:1	c.-171C>T		5_prime_UTR	Exon 1 of 6	ENSP00000374589.2
	MS4A1	ENST00000532073.5	TSL:1	c.-16-155C>T		intron	N/A	ENSP00000433519.1

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

GnomAD2 exomes AF: 0.0202 AC: 2862 AN: 141792 AF XY: 0.0164

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 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

African (AFR) AF: 0.00114 AC: 19 AN: 16628

American (AMR) AF: 0.0929 AC: 3184 AN: 34286

Ashkenazi Jewish (ASJ) AF: 0.0000501 AC: 1 AN: 19942

East Asian (EAS) AF: 0.0270 AC: 842 AN: 31128

South Asian (SAS) AF: 0.00221 AC: 140 AN: 63288

European-Finnish (FIN) AF: 0.000150 AC: 5 AN: 33266

Middle Eastern (MID) AF: 0.000241 AC: 1 AN: 4142

European-Non Finnish (NFE) AF: 0.000645 AC: 237 AN: 367310

Other (OTH) AF: 0.00927 AC: 292 AN: 31510

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

African (AFR) AF: 0.00173 AC: 72 AN: 41550

American (AMR) AF: 0.0866 AC: 1324 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.0356 AC: 184 AN: 5164

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4824

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000676 AC: 46 AN: 68024

Other (OTH) AF: 0.00994 AC: 21 AN: 2112

Alfa AF: 0.00729 Hom.: 45

Bravo AF: 0.0161

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jun 20, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.9
DANN	Benign	0.51
PhyloP100		-0.13
PromoterAI		-0.050	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17155019; hg19: chr11-60229677;