rs10665

Positions:

• chr13-113098517-A-G
• chr13-113098517-A-T

Variant summary

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

The NM_001112732.3(MCF2L):​c.*1658A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,240 control chromosomes in the GnomAD database, including 1,241 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 0.12 (1241 hom., cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MCF2L NM_001112732.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.894

Genes affected

MCF2L (HGNC:14576): (MCF.2 cell line derived transforming sequence like) This gene encodes a guanine nucleotide exchange factor that interacts specifically with the GTP-bound Rac1 and plays a role in the Rho/Rac signaling pathways. A variant in this gene was associated with osteoarthritis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCF2L	NM_001112732.3	c.*1658A>G		3_prime_UTR_variant	30/30	ENST00000535094.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCF2L	ENST00000535094.7	c.*1658A>G		3_prime_UTR_variant	30/30	2	NM_001112732.3	A1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18480 AN: 152122 Hom.: 1243 Cov.: 34

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.0337

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.0715

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.137

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 30 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 16

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.121 AC: 18482 AN: 152240 Hom.: 1241 Cov.: 34 AF XY: 0.121 AC XY: 9013 AN XY: 74436

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.0337

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.0715

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.135

Alfa AF: 0.124 Hom.: 1679

Bravo AF: 0.124

Asia WGS AF: 0.150 AC: 522 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	12
DANN	Benign	0.71

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: rs10665; hg19: chr13-113752831;