11-60394178-T-C

Variant names:

• chr11-60394178-T-C
• rs1892
• NM_021201.5:c.*317T>C

Variant summary

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

The NM_021201.5(MS4A7):​c.*317T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.753 in 205,926 control chromosomes in the GnomAD database, including 58,579 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 0.76 (43661 hom., cov: 31)
  • Exomes 𝑓: 0.74 (14918 hom.)
• Consequence: MS4A7 NM_021201.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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]

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MS4A7	NM_021201.5	c.*317T>C		3_prime_UTR_variant	Exon 7 of 7	ENST00000300184.8	NP_067024.1
MS4A7	NM_206939.2	c.*317T>C		3_prime_UTR_variant	Exon 7 of 7		NP_996822.1
MS4A7	NM_206938.2	c.*317T>C		3_prime_UTR_variant	Exon 6 of 6		NP_996821.1
MS4A7	NM_206940.2	c.*317T>C		3_prime_UTR_variant	Exon 6 of 6		NP_996823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MS4A7	ENST00000300184.8	c.*317T>C		3_prime_UTR_variant	Exon 7 of 7	1	NM_021201.5	ENSP00000300184.3

Frequencies

GnomAD3 genomes AF: 0.757 AC: 114935 AN: 151894 Hom.: 43615 Cov.: 31

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.736

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.750

Gnomad EAS AF: 0.730

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.728

Gnomad OTH AF: 0.788

GnomAD4 exome AF: 0.744 AC: 40111 AN: 53914 Hom.: 14918 Cov.: 0 AF XY: 0.744 AC XY: 20393 AN XY: 27412

Gnomad4 AFR exome AF: 0.811

Gnomad4 AMR exome AF: 0.836

Gnomad4 ASJ exome AF: 0.739

Gnomad4 EAS exome AF: 0.756

Gnomad4 SAS exome AF: 0.779

Gnomad4 FIN exome AF: 0.683

Gnomad4 NFE exome AF: 0.737

Gnomad4 OTH exome AF: 0.745

GnomAD4 genome AF: 0.757 AC: 115038 AN: 152012 Hom.: 43661 Cov.: 31 AF XY: 0.755 AC XY: 56084 AN XY: 74298

Gnomad4 AFR AF: 0.806

Gnomad4 AMR AF: 0.813

Gnomad4 ASJ AF: 0.750

Gnomad4 EAS AF: 0.730

Gnomad4 SAS AF: 0.771

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.728

Gnomad4 OTH AF: 0.786

Alfa AF: 0.748 Hom.: 38748

Bravo AF: 0.770

Asia WGS AF: 0.755 AC: 2627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.71
DANN	Benign	0.57

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: rs1892; hg19: chr11-60161651; COSMIC: COSV55731859; COSMIC: COSV55731859;