13-113098517-A-G

Variant names:

• chr13-113098517-A-G
• rs10665
• ENST00000469415.1:n.2996A>G

Variant summary

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

The ENST00000469415.1(MCF2L):​n.2996A>G variant causes a non coding transcript exon 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 ENST00000469415.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.894
• Publications: 30 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=-0.68).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000469415.1. 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.*1658A>G		3_prime_UTR	Exon 30 of 30	NP_001106203.2
	MCF2L	NM_001438390.1		c.*1658A>G		3_prime_UTR	Exon 32 of 32	NP_001425319.1
	MCF2L	NM_001438391.1		c.*1658A>G		3_prime_UTR	Exon 33 of 33	NP_001425320.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCF2L	ENST00000469415.1	TSL:1	n.2996A>G		non_coding_transcript_exon	Exon 4 of 4
	MCF2L	ENST00000535094.7	TSL:2 MANE Select	c.*1658A>G		3_prime_UTR	Exon 30 of 30	ENSP00000440374.2
	MCF2L	ENST00000488765.1	TSL:2	n.3176A>G		non_coding_transcript_exon	Exon 2 of 2

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

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: 0.00 AC: 0 AN: 26

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.121 AC: 5041 AN: 41528

American (AMR) AF: 0.120 AC: 1832 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 651 AN: 3470

East Asian (EAS) AF: 0.0337 AC: 175 AN: 5186

South Asian (SAS) AF: 0.275 AC: 1325 AN: 4826

European-Finnish (FIN) AF: 0.0715 AC: 758 AN: 10596

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8191 AN: 68010

Other (OTH) AF: 0.135 AC: 286 AN: 2116

Alfa AF: 0.123 Hom.: 4299

Bravo AF: 0.124

Asia WGS AF: 0.150 AC: 522 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	12
DANN	Benign	0.71
PhyloP100		0.89
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: rs10665; hg19: chr13-113752831;