rs2076501

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-139615087-A-C
• chrX-139615087-A-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 6 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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>G		intron	N/A	NP_001165347.1	P10911-5
	MCF2	NM_001099855.2		c.1372-35T>G		intron	N/A	NP_001093325.1	P10911-3
	MCF2	NM_001171879.2		c.1192-35T>G		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>G		intron	N/A	ENSP00000430276.1	P10911-5
	MCF2	ENST00000338585.6	TSL:1	c.1192-35T>G		intron	N/A	ENSP00000342204.6	P10911-4
	MCF2	ENST00000370576.9	TSL:1	c.1192-35T>G		intron	N/A	ENSP00000359608.4	P10911-1

Frequencies

GnomAD3 genomes AF: 0.542 AC: 59845 AN: 110357 Hom.: 12116 Cov.: 23

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

GnomAD2 exomes AF: 0.473 AC: 78455 AN: 166022 AF XY: 0.471

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 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

African (AFR) AF: 0.687 AC: 16916 AN: 24612

American (AMR) AF: 0.390 AC: 12923 AN: 33134

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 10606 AN: 18196

East Asian (EAS) AF: 0.183 AC: 5422 AN: 29563

South Asian (SAS) AF: 0.268 AC: 12984 AN: 48396

European-Finnish (FIN) AF: 0.579 AC: 23201 AN: 40093

Middle Eastern (MID) AF: 0.549 AC: 2135 AN: 3891

European-Non Finnish (NFE) AF: 0.547 AC: 421738 AN: 771145

Other (OTH) AF: 0.505 AC: 21718 AN: 42999

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

African (AFR) AF: 0.664 AC: 20188 AN: 30412

American (AMR) AF: 0.476 AC: 4938 AN: 10372

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1473 AN: 2609

East Asian (EAS) AF: 0.163 AC: 574 AN: 3515

South Asian (SAS) AF: 0.227 AC: 592 AN: 2609

European-Finnish (FIN) AF: 0.561 AC: 3274 AN: 5831

Middle Eastern (MID) AF: 0.591 AC: 127 AN: 215

European-Non Finnish (NFE) AF: 0.525 AC: 27630 AN: 52662

Other (OTH) AF: 0.522 AC: 788 AN: 1509

Alfa AF: 0.527 Hom.: 63916

Bravo AF: 0.540

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.1
DANN	Benign	0.65
PhyloP100		-0.34
PromoterAI		0.0064	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2076501; hg19: chrX-138697246; COSMIC: COSV58483517; COSMIC: COSV58483517;