13-113040195-A-G

Variant names:

• chr13-113040195-A-G
• rs11842874
• NM_001112732.3:c.279-5076A>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.279-5076A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,236 control chromosomes in the GnomAD database, including 1,405 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 (1405 hom., cov: 33)
• Consequence: MCF2L NM_001112732.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93
• Publications: 42 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 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.279-5076A>G		intron	N/A	NP_001106203.2
	MCF2L	NM_001438390.1		c.378-5076A>G		intron	N/A	NP_001425319.1
	MCF2L	NM_001438391.1		c.369-5076A>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.279-5076A>G		intron	N/A	ENSP00000440374.2
	MCF2L	ENST00000421756.5	TSL:1	c.291-5076A>G		intron	N/A	ENSP00000397285.1
	MCF2L	ENST00000375597.8	TSL:1	c.273-5076A>G		intron	N/A	ENSP00000364747.4

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17809 AN: 152118 Hom.: 1400 Cov.: 33

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.0688

Gnomad ASJ AF: 0.0519

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.0648

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0716

Gnomad OTH AF: 0.113

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.117 AC: 17855 AN: 152236 Hom.: 1405 Cov.: 33 AF XY: 0.118 AC XY: 8759 AN XY: 74432

African (AFR) AF: 0.217 AC: 9021 AN: 41504

American (AMR) AF: 0.0687 AC: 1052 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0519 AC: 180 AN: 3470

East Asian (EAS) AF: 0.181 AC: 936 AN: 5168

South Asian (SAS) AF: 0.0644 AC: 311 AN: 4826

European-Finnish (FIN) AF: 0.108 AC: 1151 AN: 10620

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0716 AC: 4869 AN: 68024

Other (OTH) AF: 0.118 AC: 249 AN: 2116

Alfa AF: 0.0856 Hom.: 3260

Bravo AF: 0.122

Asia WGS AF: 0.156 AC: 542 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.66
DANN	Benign	0.33
PhyloP100		-1.9
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: rs11842874; hg19: chr13-113694509;