X-139615164-T-C

Variant names:

• chrX-139615164-T-C
• rs2076502
• NM_001171876.2:c.1372-112A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001171876.2(MCF2):​c.1372-112A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0373 in 560,903 control chromosomes in the GnomAD database, including 828 homozygotes. There are 6,064 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 0.068 (401 hom., 2142 hem., cov: 23)
  • Exomes 𝑓: 0.030 (427 hom. 3922 hem.)
• Consequence: MCF2 NM_001171876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.37
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.175 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCF2	NM_001171876.2	MANE Select	c.1372-112A>G		intron	N/A	NP_001165347.1	P10911-5
	MCF2	NM_001099855.2		c.1372-112A>G		intron	N/A	NP_001093325.1	P10911-3
	MCF2	NM_001171879.2		c.1192-112A>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.1372-112A>G		intron	N/A	ENSP00000430276.1	P10911-5
	MCF2	ENST00000338585.6	TSL:1	c.1192-112A>G		intron	N/A	ENSP00000342204.6	P10911-4
	MCF2	ENST00000370576.9	TSL:1	c.1192-112A>G		intron	N/A	ENSP00000359608.4	P10911-1

Frequencies

GnomAD3 genomes AF: 0.0677 AC: 7560 AN: 111709 Hom.: 401 Cov.: 23

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0728

Gnomad ASJ AF: 0.00644

Gnomad EAS AF: 0.0852

Gnomad SAS AF: 0.0245

Gnomad FIN AF: 0.0198

Gnomad MID AF: 0.0209

Gnomad NFE AF: 0.0128

Gnomad OTH AF: 0.0637

GnomAD4 exome AF: 0.0298 AC: 13377 AN: 449143 Hom.: 427 AF XY: 0.0314 AC XY: 3922 AN XY: 124843

African (AFR) AF: 0.201 AC: 2407 AN: 11991

American (AMR) AF: 0.0753 AC: 1464 AN: 19452

Ashkenazi Jewish (ASJ) AF: 0.00584 AC: 65 AN: 11122

East Asian (EAS) AF: 0.123 AC: 3124 AN: 25403

South Asian (SAS) AF: 0.0328 AC: 880 AN: 26863

European-Finnish (FIN) AF: 0.0230 AC: 804 AN: 34977

Middle Eastern (MID) AF: 0.0304 AC: 54 AN: 1774

European-Non Finnish (NFE) AF: 0.0127 AC: 3740 AN: 293912

Other (OTH) AF: 0.0355 AC: 839 AN: 23649

GnomAD4 genome AF: 0.0677 AC: 7563 AN: 111760 Hom.: 401 Cov.: 23 AF XY: 0.0629 AC XY: 2142 AN XY: 34062

African (AFR) AF: 0.179 AC: 5511 AN: 30742

American (AMR) AF: 0.0726 AC: 765 AN: 10536

Ashkenazi Jewish (ASJ) AF: 0.00644 AC: 17 AN: 2640

East Asian (EAS) AF: 0.0854 AC: 303 AN: 3547

South Asian (SAS) AF: 0.0243 AC: 65 AN: 2680

European-Finnish (FIN) AF: 0.0198 AC: 121 AN: 6115

Middle Eastern (MID) AF: 0.0229 AC: 5 AN: 218

European-Non Finnish (NFE) AF: 0.0128 AC: 681 AN: 53068

Other (OTH) AF: 0.0622 AC: 95 AN: 1527

Alfa AF: 0.0307 Hom.: 230

Bravo AF: 0.0789

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.078
DANN	Benign	0.57
PhyloP100		-2.4
PromoterAI		0.0014	Neutral
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: rs2076502; hg19: chrX-138697323; COSMIC: COSV58491775; COSMIC: COSV58491775;