rs17681175

Positions:

• chr10-119844062-G-A
• chr10-119844062-G-T

Variant summary

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

The NM_001256378.2(MCMBP):​c.828-636C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,200 control chromosomes in the GnomAD database, including 956 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 0.11 (956 hom., cov: 32)
• Consequence: MCMBP NM_001256378.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.301

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCMBP	NM_001256378.2	c.828-636C>T		intron_variant		ENST00000369077.4	NP_001243307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCMBP	ENST00000369077.4	c.828-636C>T		intron_variant		1	NM_001256378.2	ENSP00000358073	P3
MCMBP	ENST00000360003.7	c.828-636C>T		intron_variant		2		ENSP00000353098	A1
MCMBP	ENST00000466047.5	n.930-636C>T		intron_variant, non_coding_transcript_variant		2
MCMBP	ENST00000495407.1	n.1299-636C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16589 AN: 152082 Hom.: 953 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0954

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.0594

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.104

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.109 AC: 16594 AN: 152200 Hom.: 956 Cov.: 32 AF XY: 0.107 AC XY: 7977 AN XY: 74424

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.0953

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.00173

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.0594

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.103

Alfa AF: 0.119 Hom.: 553

Bravo AF: 0.110

Asia WGS AF: 0.0660 AC: 230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.8
DANN	Benign	0.46

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: rs17681175; hg19: chr10-121603574; COSMIC: COSV63508449;