rs2273747

Positions:

• chr10-119831999-G-A

Variant summary

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

The NM_001256378.2(MCMBP):​c.1796+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,602,792 control chromosomes in the GnomAD database, including 30,832 homozygotes. 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 0.17 (2288 hom., cov: 32)
  • Exomes 𝑓: 0.19 (28544 hom.)
• Consequence: MCMBP NM_001256378.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.724

Genes affected

MCMBP (HGNC:25782): (minichromosome maintenance complex binding protein) This gene encodes a protein which is a component of the hexameric minichromosome maintenance (MCM) complex which regulates initiation and elongation of DNA. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCMBP	NM_001256378.2	c.1796+13C>T		intron_variant		ENST00000369077.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCMBP	ENST00000369077.4	c.1796+13C>T		intron_variant		1	NM_001256378.2	P3
MCMBP	ENST00000360003.7	c.1802+13C>T		intron_variant		2		A1
MCMBP	ENST00000466047.5	n.1898+13C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25366 AN: 151990 Hom.: 2284 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.149

GnomAD3 exomes AF: 0.196 AC: 47653 AN: 243352 Hom.: 5656 AF XY: 0.210 AC XY: 27729 AN XY: 131734

Gnomad AFR exome AF: 0.142

Gnomad AMR exome AF: 0.120

Gnomad ASJ exome AF: 0.196

Gnomad EAS exome AF: 0.185

Gnomad SAS exome AF: 0.437

Gnomad FIN exome AF: 0.154

Gnomad NFE exome AF: 0.173

Gnomad OTH exome AF: 0.187

GnomAD4 exome AF: 0.187 AC: 271047 AN: 1450684 Hom.: 28544 Cov.: 30 AF XY: 0.195 AC XY: 140835 AN XY: 721490

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.121

Gnomad4 ASJ exome AF: 0.187

Gnomad4 EAS exome AF: 0.182

Gnomad4 SAS exome AF: 0.432

Gnomad4 FIN exome AF: 0.153

Gnomad4 NFE exome AF: 0.173

Gnomad4 OTH exome AF: 0.196

GnomAD4 genome AF: 0.167 AC: 25382 AN: 152108 Hom.: 2288 Cov.: 32 AF XY: 0.170 AC XY: 12669 AN XY: 74358

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.149

Alfa AF: 0.187 Hom.: 1556

Bravo AF: 0.157

Asia WGS AF: 0.269 AC: 938 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.045
DANN	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2273747; hg19: chr10-121591511; COSMIC: COSV62820243; COSMIC: COSV62820243;