rs10521799

Variant names:

• chrX-139603353-T-A
• rs10521799
• NM_001171876.2:c.1972-855A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001171876.2. 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
	MCF2	NM_001171876.2	MANE Select	c.1972-855A>T		intron	N/A	NP_001165347.1
	MCF2	NM_001099855.2		c.1924-855A>T		intron	N/A	NP_001093325.1
	MCF2	NM_001171879.2		c.1792-855A>T		intron	N/A	NP_001165350.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCF2	ENST00000519895.6	TSL:2 MANE Select	c.1972-855A>T		intron	N/A	ENSP00000430276.1
	MCF2	ENST00000338585.6	TSL:1	c.1792-855A>T		intron	N/A	ENSP00000342204.6
	MCF2	ENST00000370576.9	TSL:1	c.1744-855A>T		intron	N/A	ENSP00000359608.4

Frequencies

GnomAD3 genomes AF: 0.0409 AC: 4580 AN: 111974 Hom.: 115 Cov.: 23

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

African (AFR) AF: 0.0879 AC: 2711 AN: 30832

American (AMR) AF: 0.0597 AC: 632 AN: 10581

Ashkenazi Jewish (ASJ) AF: 0.00604 AC: 16 AN: 2650

East Asian (EAS) AF: 0.0826 AC: 292 AN: 3533

South Asian (SAS) AF: 0.0266 AC: 71 AN: 2665

European-Finnish (FIN) AF: 0.0194 AC: 118 AN: 6089

Middle Eastern (MID) AF: 0.0274 AC: 6 AN: 219

European-Non Finnish (NFE) AF: 0.0126 AC: 673 AN: 53249

Other (OTH) AF: 0.0407 AC: 62 AN: 1522

Alfa AF: 0.0295 Hom.: 132

Bravo AF: 0.0473

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.46
PhyloP100		-0.31
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: rs10521799; hg19: chrX-138685512;