X-139615087-A-G

Variant names:

• chrX-139615087-A-G
• rs2076501
• NM_001171876.2:c.1372-35T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001171876.2(MCF2):​c.1372-35T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000987 in 1,012,768 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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: not found (cov: 23)
  • Exomes 𝑓: 9.9e-7 (0 hom. 0 hem.)
• Consequence: MCF2 NM_001171876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCF2	NM_001171876.2	MANE Select	c.1372-35T>C		intron	N/A	NP_001165347.1	P10911-5
	MCF2	NM_001099855.2		c.1372-35T>C		intron	N/A	NP_001093325.1	P10911-3
	MCF2	NM_001171879.2		c.1192-35T>C		intron	N/A	NP_001165350.1	P10911-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCF2	ENST00000519895.6	TSL:2 MANE Select	c.1372-35T>C		intron	N/A	ENSP00000430276.1	P10911-5
	MCF2	ENST00000338585.6	TSL:1	c.1192-35T>C		intron	N/A	ENSP00000342204.6	P10911-4
	MCF2	ENST00000370576.9	TSL:1	c.1192-35T>C		intron	N/A	ENSP00000359608.4	P10911-1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.87e-7 AC: 1 AN: 1012768 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 296866

African (AFR) AF: 0.00 AC: 0 AN: 24630

American (AMR) AF: 0.00 AC: 0 AN: 33160

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18205

East Asian (EAS) AF: 0.0000338 AC: 1 AN: 29569

South Asian (SAS) AF: 0.00 AC: 0 AN: 48424

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40100

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3892

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 771767

Other (OTH) AF: 0.00 AC: 0 AN: 43021

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.1
DANN	Benign	0.73
PhyloP100		-0.34
PromoterAI		-0.0065	Neutral

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: rs2076501; hg19: chrX-138697246;