13-113098850-T-C

Variant names:

• chr13-113098850-T-C
• rs2181540
• NM_001112732.3:c.*1991T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001112732.3(MCF2L):​c.*1991T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,016 control chromosomes in the GnomAD database, including 1,823 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 0.15 (1821 hom., cov: 34)
  • Exomes 𝑓: 0.14 (2 hom.)
• Consequence: MCF2L NM_001112732.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92
• Publications: 18 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.264 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.*1991T>C		3_prime_UTR	Exon 30 of 30	NP_001106203.2
	MCF2L	NM_001438390.1		c.*1991T>C		3_prime_UTR	Exon 32 of 32	NP_001425319.1
	MCF2L	NM_001438391.1		c.*1991T>C		3_prime_UTR	Exon 33 of 33	NP_001425320.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCF2L	ENST00000535094.7	TSL:2 MANE Select	c.*1991T>C		3_prime_UTR	Exon 30 of 30	ENSP00000440374.2
	MCF2L	ENST00000420013.6	TSL:4	c.*1991T>C		3_prime_UTR	Exon 31 of 31	ENSP00000404422.2
	MCF2L	ENST00000375604.6	TSL:2	c.*1991T>C		3_prime_UTR	Exon 30 of 30	ENSP00000364754.3

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22154 AN: 151812 Hom.: 1816 Cov.: 34

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.0380

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.0725

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.156

GnomAD4 exome AF: 0.143 AC: 12 AN: 84 Hom.: 2 Cov.: 0 AF XY: 0.140 AC XY: 7 AN XY: 50

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0714 AC: 3 AN: 42

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.227 AC: 5 AN: 22

Other (OTH) AF: 0.222 AC: 4 AN: 18

GnomAD4 genome AF: 0.146 AC: 22183 AN: 151932 Hom.: 1821 Cov.: 34 AF XY: 0.145 AC XY: 10781 AN XY: 74250

African (AFR) AF: 0.198 AC: 8204 AN: 41400

American (AMR) AF: 0.136 AC: 2084 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 665 AN: 3466

East Asian (EAS) AF: 0.0381 AC: 197 AN: 5176

South Asian (SAS) AF: 0.277 AC: 1331 AN: 4810

European-Finnish (FIN) AF: 0.0725 AC: 765 AN: 10548

Middle Eastern (MID) AF: 0.250 AC: 73 AN: 292

European-Non Finnish (NFE) AF: 0.123 AC: 8379 AN: 67956

Other (OTH) AF: 0.155 AC: 326 AN: 2104

Alfa AF: 0.134 Hom.: 3460

Bravo AF: 0.150

Asia WGS AF: 0.164 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.30
DANN	Benign	0.53
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: rs2181540; hg19: chr13-113753164;