rs1755693

Positions:

• chr13-113084489-A-G

Variant summary

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

The NM_001112732.3(MCF2L):​c.2062-403A>G 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 305,342 control chromosomes in the GnomAD database, including 60,151 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 0.61 (29006 hom., cov: 34)
  • Exomes 𝑓: 0.63 (31145 hom.)
• Consequence: MCF2L NM_001112732.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.57

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=-1.13).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCF2L	NM_001112732.3	c.2062-403A>G		intron_variant		ENST00000535094.7	NP_001106203.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCF2L	ENST00000535094.7	c.2062-403A>G		intron_variant		2	NM_001112732.3	ENSP00000440374.2

Frequencies

GnomAD3 genomes AF: 0.612 AC: 93121 AN: 152080 Hom.: 28995 Cov.: 34

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.638

GnomAD4 exome AF: 0.629 AC: 96318 AN: 153144 Hom.: 31145 AF XY: 0.627 AC XY: 48893 AN XY: 77994

Gnomad4 AFR exome AF: 0.479

Gnomad4 AMR exome AF: 0.539

Gnomad4 ASJ exome AF: 0.674

Gnomad4 EAS exome AF: 0.460

Gnomad4 SAS exome AF: 0.585

Gnomad4 FIN exome AF: 0.653

Gnomad4 NFE exome AF: 0.662

Gnomad4 OTH exome AF: 0.622

GnomAD4 genome AF: 0.612 AC: 93161 AN: 152198 Hom.: 29006 Cov.: 34 AF XY: 0.611 AC XY: 45440 AN XY: 74416

Gnomad4 AFR AF: 0.504

Gnomad4 AMR AF: 0.587

Gnomad4 ASJ AF: 0.697

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.622

Gnomad4 FIN AF: 0.664

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.642

Alfa AF: 0.649 Hom.: 4050

Bravo AF: 0.596

Asia WGS AF: 0.566 AC: 1966 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.39
DANN	Benign	0.31

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: rs1755693; hg19: chr13-113738803;