11-60394178-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021201.5. 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
	MS4A7	NM_021201.5	MANE Select	c.*317T>C		3_prime_UTR	Exon 7 of 7	NP_067024.1
	MS4A7	NM_206939.2		c.*317T>C		3_prime_UTR	Exon 7 of 7	NP_996822.1
	MS4A7	NM_206938.2		c.*317T>C		3_prime_UTR	Exon 6 of 6	NP_996821.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A7	ENST00000300184.8	TSL:1 MANE Select	c.*317T>C		3_prime_UTR	Exon 7 of 7	ENSP00000300184.3
	MS4A7	ENST00000358246.5	TSL:3	c.*317T>C		3_prime_UTR	Exon 6 of 6	ENSP00000350983.1
	MS4A7	ENST00000534016.5	TSL:2	c.*317T>C		3_prime_UTR	Exon 6 of 6	ENSP00000434637.1

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

African (AFR) AF: 0.811 AC: 1560 AN: 1924

American (AMR) AF: 0.836 AC: 1511 AN: 1808

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 1752 AN: 2372

East Asian (EAS) AF: 0.756 AC: 2720 AN: 3598

South Asian (SAS) AF: 0.779 AC: 943 AN: 1210

European-Finnish (FIN) AF: 0.683 AC: 1700 AN: 2488

Middle Eastern (MID) AF: 0.808 AC: 236 AN: 292

European-Non Finnish (NFE) AF: 0.737 AC: 26861 AN: 36428

Other (OTH) AF: 0.745 AC: 2828 AN: 3794

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

African (AFR) AF: 0.806 AC: 33430 AN: 41466

American (AMR) AF: 0.813 AC: 12425 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 2603 AN: 3470

East Asian (EAS) AF: 0.730 AC: 3767 AN: 5160

South Asian (SAS) AF: 0.771 AC: 3711 AN: 4812

European-Finnish (FIN) AF: 0.671 AC: 7083 AN: 10554

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.728 AC: 49449 AN: 67958

Other (OTH) AF: 0.786 AC: 1660 AN: 2112

Alfa AF: 0.750 Hom.: 51909

Bravo AF: 0.770

Asia WGS AF: 0.755 AC: 2627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.71
DANN	Benign	0.57
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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