rs10521799

chrX-139603353-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001171876.2(MCF2):c.1972-855A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0409 in 112,026 control chromosomes in the GnomAD database, including 115 homozygotes. There are 1,316 hemizygotes in GnomAD. 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 0.041 (115 hom., 1316 hem., cov: 23)
• Consequence: MCF2 NM_001171876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.313

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCF2	NM_001171876.2	c.1972-855A>T		intron_variant		ENST00000519895.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCF2	ENST00000519895.6	c.1972-855A>T		intron_variant		2	NM_001171876.2	P4

Frequencies

GnomAD3 genomes AF: 0.0409 AC: 4580 AN: 111974 Hom.: 115 Cov.: 23 AF XY: 0.0383 AC XY: 1309 AN XY: 34164

Gnomad AFR AF: 0.0879

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0599

Gnomad ASJ AF: 0.00604

Gnomad EAS AF: 0.0824

Gnomad SAS AF: 0.0269

Gnomad FIN AF: 0.0194

Gnomad MID AF: 0.0333

Gnomad NFE AF: 0.0126

Gnomad OTH AF: 0.0419

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

GnomAD4 genome AF: 0.0409 AC: 4581 AN: 112026 Hom.: 115 Cov.: 23 AF XY: 0.0385 AC XY: 1316 AN XY: 34226

Gnomad4 AFR AF: 0.0879

Gnomad4 AMR AF: 0.0597

Gnomad4 ASJ AF: 0.00604

Gnomad4 EAS AF: 0.0826

Gnomad4 SAS AF: 0.0266

Gnomad4 FIN AF: 0.0194

Gnomad4 NFE AF: 0.0126

Gnomad4 OTH AF: 0.0407

Alfa AF: 0.0295 Hom.: 132

Bravo AF: 0.0473

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.1
Dann	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs10521799; hg19: chrX-138685512;