rs7914

Variant names:

• chr11-119309606-G-A
• rs7914
• NM_006500.3:c.*280C>T

Variant summary

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

The NM_006500.3(MCAM):​c.*280C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 515,812 control chromosomes in the GnomAD database, including 23,025 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 0.29 (6752 hom., cov: 33)
  • Exomes 𝑓: 0.28 (16273 hom.)
• Consequence: MCAM NM_006500.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182

Genes affected

MCAM (HGNC:6934): (melanoma cell adhesion molecule) Involved in glomerular filtration and vascular wound healing. Acts upstream of or within angiogenesis. Located in external side of plasma membrane. Biomarker of chronic obstructive pulmonary disease and uveal melanoma. [provided by Alliance of Genome Resources, Apr 2022]

CBL (HGNC:1541): (Cbl proto-oncogene) This gene is a proto-oncogene that encodes a RING finger E3 ubiquitin ligase. The encoded protein is one of the enzymes required for targeting substrates for degradation by the proteasome. This protein mediates the transfer of ubiquitin from ubiquitin conjugating enzymes (E2) to specific substrates. This protein also contains an N-terminal phosphotyrosine binding domain that allows it to interact with numerous tyrosine-phosphorylated substrates and target them for proteasome degradation. As such it functions as a negative regulator of many signal transduction pathways. This gene has been found to be mutated or translocated in many cancers including acute myeloid leukaemia, and expansion of CGG repeats in the 5' UTR has been associated with Jacobsen syndrome. Mutations in this gene are also the cause of Noonan syndrome-like disorder. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCAM	NM_006500.3	c.*280C>T		3_prime_UTR_variant	Exon 16 of 16	ENST00000264036.6	NP_006491.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCAM	ENST00000264036	c.*280C>T		3_prime_UTR_variant	Exon 16 of 16	1	NM_006500.3	ENSP00000264036.4

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43725 AN: 151990 Hom.: 6748 Cov.: 33

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.274

GnomAD4 exome AF: 0.278 AC: 101013 AN: 363704 Hom.: 16273 Cov.: 0 AF XY: 0.290 AC XY: 55022 AN XY: 189798

Gnomad4 AFR exome AF: 0.363

Gnomad4 AMR exome AF: 0.285

Gnomad4 ASJ exome AF: 0.281

Gnomad4 EAS exome AF: 0.423

Gnomad4 SAS exome AF: 0.520

Gnomad4 FIN exome AF: 0.228

Gnomad4 NFE exome AF: 0.226

Gnomad4 OTH exome AF: 0.276

GnomAD4 genome AF: 0.288 AC: 43768 AN: 152108 Hom.: 6752 Cov.: 33 AF XY: 0.292 AC XY: 21746 AN XY: 74354

Gnomad4 AFR AF: 0.351

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.274

Alfa AF: 0.253 Hom.: 6846

Bravo AF: 0.293

Asia WGS AF: 0.498 AC: 1730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	2.6
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs7914; hg19: chr11-119180316;