11-60387527-T-C

Position:

• chr11-60387527-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021201.5(MS4A7):​c.339+754T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 151,942 control chromosomes in the GnomAD database, including 29,478 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 0.62 (29478 hom., cov: 31)
• Consequence: MS4A7 NM_021201.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

Genes affected

MS4A7 (HGNC:13378): (membrane spanning 4-domains A7) This gene encodes a member of the membrane-spanning 4A gene family, members of which are characterized by common structural features and similar intron/exon splice boundaries and display unique expression patterns in hematopoietic cells and nonlymphoid tissues. This family member is associated with mature cellular function in the monocytic lineage, and it may be a component of a receptor complex involved in signal transduction. This gene is localized to 11q12, in a cluster of other family members. At least four alternatively spliced transcript variants encoding two distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

MS4A7 (HGNC:):

MS4A14 (HGNC:30706): (membrane spanning 4-domains A14) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MS4A6E (HGNC:14285): (membrane spanning 4-domains A6E) 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. The gene encoding this protein is localized to 11q12.3, among a cluster of family members. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MS4A7	NM_021201.5	c.339+754T>C		intron_variant		ENST00000300184.8	NP_067024.1
MS4A7	NM_206939.2	c.339+754T>C		intron_variant			NP_996822.1
MS4A7	NM_206938.2	c.204+754T>C		intron_variant			NP_996821.1
MS4A7	NM_206940.2	c.204+754T>C		intron_variant			NP_996823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MS4A7	ENST00000300184.8	c.339+754T>C		intron_variant		1	NM_021201.5	ENSP00000300184.3

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94242 AN: 151824 Hom.: 29444 Cov.: 31

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.645

Gnomad OTH AF: 0.671

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

GnomAD4 genome AF: 0.621 AC: 94334 AN: 151942 Hom.: 29478 Cov.: 31 AF XY: 0.618 AC XY: 45888 AN XY: 74260

Gnomad4 AFR AF: 0.557

Gnomad4 AMR AF: 0.660

Gnomad4 ASJ AF: 0.708

Gnomad4 EAS AF: 0.631

Gnomad4 SAS AF: 0.589

Gnomad4 FIN AF: 0.622

Gnomad4 NFE AF: 0.645

Gnomad4 OTH AF: 0.671

Alfa AF: 0.636 Hom.: 5139

Bravo AF: 0.626

Asia WGS AF: 0.607 AC: 2113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.22
DANN	Benign	0.44

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: rs7935082; hg19: chr11-60155000;