rs2076501

chrX-139615087-A-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001171876.2(MCF2):c.1372-35T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.54 (12111 hom., 17351 hem., cov: 23)
  • Exomes 𝑓: 0.52 (97243 hom. 160302 hem.)
  • Failed GnomAD Quality Control
• Consequence: MCF2 NM_001171876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341

Genes affected

MCF2 (HGNC:6940): (MCF.2 cell line derived transforming sequence) The oncogenic protein encoded by this gene is a guanine nucleotide exchange factor (GEF) that exerts control over some members of the Rho family of small GTPases. Several transcript variants encoding different isoforms have been found for this gene. These isoforms exhibit different expression patterns and varying levels of GEF activity.[provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant X-139615087-A-C is Benign according to our data. Variant chrX-139615087-A-C is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAd at 12116 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCF2	NM_001171876.2	c.1372-35T>G		intron_variant		ENST00000519895.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCF2	ENST00000519895.6	c.1372-35T>G		intron_variant		2	NM_001171876.2	P4

Frequencies

GnomAD3 genomes AF: 0.542 AC: 59845 AN: 110357 Hom.: 12116 Cov.: 23 AF XY: 0.529 AC XY: 17310 AN XY: 32733

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.593

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.528

GnomAD3 exomes AF: 0.473 AC: 78455 AN: 166022 Hom.: 13834 AF XY: 0.471 AC XY: 25446 AN XY: 54028

Gnomad AFR exome AF: 0.677

Gnomad AMR exome AF: 0.375

Gnomad ASJ exome AF: 0.575

Gnomad EAS exome AF: 0.164

Gnomad SAS exome AF: 0.255

Gnomad FIN exome AF: 0.582

Gnomad NFE exome AF: 0.535

Gnomad OTH exome AF: 0.478

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.521 AC: 527643 AN: 1012029 Hom.: 97243 Cov.: 18 AF XY: 0.540 AC XY: 160302 AN XY: 296797

Gnomad4 AFR exome AF: 0.687

Gnomad4 AMR exome AF: 0.390

Gnomad4 ASJ exome AF: 0.583

Gnomad4 EAS exome AF: 0.183

Gnomad4 SAS exome AF: 0.268

Gnomad4 FIN exome AF: 0.579

Gnomad4 NFE exome AF: 0.547

Gnomad4 OTH exome AF: 0.505

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.542 AC: 59872 AN: 110408 Hom.: 12111 Cov.: 23 AF XY: 0.529 AC XY: 17351 AN XY: 32794

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.476

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.561

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.522

Alfa AF: 0.519 Hom.: 50232

Bravo AF: 0.540

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	8.1
Dann	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2076501; hg19: chrX-138697246; COSMIC: COSV58483517; COSMIC: COSV58483517;