11-60462414-GCA-ACC

Variant names:

• chr11-60462414-GCA-ACC
• NM_152866.3:c.40_42delGCAinsACC
• MS4A1 p.Ala14Thr

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_152866.3(MS4A1):​c.40_42delGCAinsACC​(p.Ala14Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Synonymous variant affecting the same amino acid position (i.e. A14A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MS4A1 NM_152866.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.398
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A1	NM_152866.3	MANE Select	c.40_42delGCAinsACC	p.Ala14Thr	missense	N/A	NP_690605.1	P11836-1
	MS4A1	NM_021950.4		c.40_42delGCAinsACC	p.Ala14Thr	missense	N/A	NP_068769.2
	MS4A1	NM_152867.2		c.40_42delGCAinsACC	p.Ala14Thr	missense	N/A	NP_690606.1	P11836-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A1	ENST00000345732.9	TSL:1 MANE Select	c.40_42delGCAinsACC	p.Ala14Thr	missense	N/A	ENSP00000314620.7	P11836-1
	MS4A1	ENST00000389939.2	TSL:1	c.40_42delGCAinsACC	p.Ala14Thr	missense	N/A	ENSP00000374589.2	P11836-1
	MS4A1	ENST00000532073.5	TSL:1	c.40_42delGCAinsACC	p.Ala14Thr	missense	N/A	ENSP00000433519.1	E9PKH8

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.40

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-60229887;