rs1755693

Variant names:

• chr13-113084489-A-G
• rs1755693
• NM_001112732.3:c.2062-403A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001112732.3. 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
	MCF2L	NM_001112732.3	MANE Select	c.2062-403A>G		intron	N/A	NP_001106203.2
	MCF2L	NM_001438390.1		c.2161-403A>G		intron	N/A	NP_001425319.1
	MCF2L	NM_001438391.1		c.2152-403A>G		intron	N/A	NP_001425320.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCF2L	ENST00000535094.7	TSL:2 MANE Select	c.2062-403A>G		intron	N/A	ENSP00000440374.2
	MCF2L	ENST00000421756.5	TSL:1	c.2074-403A>G		intron	N/A	ENSP00000397285.1
	MCF2L	ENST00000375597.8	TSL:1	c.2056-403A>G		intron	N/A	ENSP00000364747.4

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

African (AFR) AF: 0.479 AC: 2507 AN: 5238

American (AMR) AF: 0.539 AC: 3327 AN: 6172

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 3454 AN: 5122

East Asian (EAS) AF: 0.460 AC: 4706 AN: 10240

South Asian (SAS) AF: 0.585 AC: 6621 AN: 11326

European-Finnish (FIN) AF: 0.653 AC: 5357 AN: 8204

Middle Eastern (MID) AF: 0.616 AC: 440 AN: 714

European-Non Finnish (NFE) AF: 0.662 AC: 63990 AN: 96622

Other (OTH) AF: 0.622 AC: 5916 AN: 9506

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

African (AFR) AF: 0.504 AC: 20944 AN: 41522

American (AMR) AF: 0.587 AC: 8978 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.697 AC: 2421 AN: 3472

East Asian (EAS) AF: 0.507 AC: 2628 AN: 5180

South Asian (SAS) AF: 0.622 AC: 3001 AN: 4824

European-Finnish (FIN) AF: 0.664 AC: 7032 AN: 10588

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 46013 AN: 68006

Other (OTH) AF: 0.642 AC: 1358 AN: 2114

Alfa AF: 0.643 Hom.: 4146

Bravo AF: 0.596

Asia WGS AF: 0.566 AC: 1966 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.39
DANN	Benign	0.31
PhyloP100		-3.6
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: rs1755693; hg19: chr13-113738803;