rs2076500

Positions:

• chrX-139614790-C-T

Variant summary

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

The NM_001171876.2(MCF2):​c.1543+91G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 841,890 control chromosomes in the GnomAD database, including 1,043 homozygotes. There are 5,600 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 0.022 (99 hom., 819 hem., cov: 23)
  • Exomes 𝑓: 0.021 (944 hom. 4781 hem.)
• Consequence: MCF2 NM_001171876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCF2	NM_001171876.2	c.1543+91G>A		intron_variant		ENST00000519895.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCF2	ENST00000519895.6	c.1543+91G>A		intron_variant		2	NM_001171876.2	P4

Frequencies

GnomAD3 genomes AF: 0.0219 AC: 2428 AN: 110853 Hom.: 97 Cov.: 23 AF XY: 0.0245 AC XY: 814 AN XY: 33197

Gnomad AFR AF: 0.00409

Gnomad AMI AF: 0.0234

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.00342

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.0333

Gnomad FIN AF: 0.0383

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00337

Gnomad OTH AF: 0.0399

GnomAD4 exome AF: 0.0213 AC: 15592 AN: 730984 Hom.: 944 AF XY: 0.0248 AC XY: 4781 AN XY: 192748

Gnomad4 AFR exome AF: 0.00252

Gnomad4 AMR exome AF: 0.189

Gnomad4 ASJ exome AF: 0.00381

Gnomad4 EAS exome AF: 0.223

Gnomad4 SAS exome AF: 0.0351

Gnomad4 FIN exome AF: 0.0390

Gnomad4 NFE exome AF: 0.00258

Gnomad4 OTH exome AF: 0.0210

GnomAD4 genome AF: 0.0220 AC: 2438 AN: 110906 Hom.: 99 Cov.: 23 AF XY: 0.0246 AC XY: 819 AN XY: 33262

Gnomad4 AFR AF: 0.00408

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.00342

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.0331

Gnomad4 FIN AF: 0.0383

Gnomad4 NFE AF: 0.00337

Gnomad4 OTH AF: 0.0388

Alfa AF: 0.0134 Hom.: 71

Bravo AF: 0.0356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.59
DANN	Benign	0.56

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: rs2076500; hg19: chrX-138696949; COSMIC: COSV58486369;