X-139614790-C-T

Variant names:

• chrX-139614790-C-T
• rs2076500
• NM_001171876.2:c.1543+91G>A

Variant summary

Our verdict is Benign. The variant received -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
• 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 (EAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCF2	NM_001171876.2	c.1543+91G>A		intron_variant	Intron 13 of 28	ENST00000519895.6	NP_001165347.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCF2	ENST00000519895.6	c.1543+91G>A		intron_variant	Intron 13 of 28	2	NM_001171876.2	ENSP00000430276.1

Frequencies

GnomAD3 genomes AF: 0.0219 AC: 2428 AN: 110853 Hom.: 97 Cov.: 23

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

African (AFR) AF: 0.00252 AC: 45 AN: 17840

American (AMR) AF: 0.189 AC: 4382 AN: 23233

Ashkenazi Jewish (ASJ) AF: 0.00381 AC: 52 AN: 13640

East Asian (EAS) AF: 0.223 AC: 6232 AN: 27989

South Asian (SAS) AF: 0.0351 AC: 1308 AN: 37265

European-Finnish (FIN) AF: 0.0390 AC: 1473 AN: 37799

Middle Eastern (MID) AF: 0.00632 AC: 18 AN: 2849

European-Non Finnish (NFE) AF: 0.00258 AC: 1387 AN: 537222

Other (OTH) AF: 0.0210 AC: 695 AN: 33147

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

African (AFR) AF: 0.00408 AC: 125 AN: 30643

American (AMR) AF: 0.113 AC: 1172 AN: 10354

Ashkenazi Jewish (ASJ) AF: 0.00342 AC: 9 AN: 2630

East Asian (EAS) AF: 0.162 AC: 566 AN: 3496

South Asian (SAS) AF: 0.0331 AC: 87 AN: 2632

European-Finnish (FIN) AF: 0.0383 AC: 226 AN: 5898

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00337 AC: 178 AN: 52831

Other (OTH) AF: 0.0388 AC: 59 AN: 1521

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
PhyloP100		0.097
PromoterAI		0.0033	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: rs2076500; hg19: chrX-138696949; COSMIC: COSV58486369;