8-6406432-G-C

Position:

• chr8-6406432-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NR_040040.1(MCPH1-DT):​n.117C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 557,098 control chromosomes in the GnomAD database, including 5,989 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (3038 hom., cov: 34)
  • Exomes 𝑓: 0.11 (2951 hom.)
• Consequence: MCPH1-DT NR_040040.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.32

Genes affected

MCPH1-DT (HGNC:55599): (MCPH1 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 8-6406432-G-C is Benign according to our data. Variant chr8-6406432-G-C is described in ClinVar as [Benign]. Clinvar id is 1238897.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCPH1-DT	NR_040040.1	n.117C>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCPH1-DT	ENST00000500118.4	n.141C>G		non_coding_transcript_exon_variant	1/2	2
MCPH1-DT	ENST00000606853.2	n.149C>G		non_coding_transcript_exon_variant	1/1
MCPH1-DT	ENST00000523225.1	n.243-61C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25669 AN: 152090 Hom.: 3025 Cov.: 34

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.0156

Gnomad SAS AF: 0.0771

Gnomad FIN AF: 0.0996

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.152

GnomAD4 exome AF: 0.108 AC: 43735 AN: 404890 Hom.: 2951 Cov.: 3 AF XY: 0.107 AC XY: 22888 AN XY: 213542

Gnomad4 AFR exome AF: 0.328

Gnomad4 AMR exome AF: 0.0845

Gnomad4 ASJ exome AF: 0.173

Gnomad4 EAS exome AF: 0.00550

Gnomad4 SAS exome AF: 0.0832

Gnomad4 FIN exome AF: 0.0887

Gnomad4 NFE exome AF: 0.113

Gnomad4 OTH exome AF: 0.130

GnomAD4 genome AF: 0.169 AC: 25715 AN: 152208 Hom.: 3038 Cov.: 34 AF XY: 0.165 AC XY: 12255 AN XY: 74444

Gnomad4 AFR AF: 0.335

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.0155

Gnomad4 SAS AF: 0.0777

Gnomad4 FIN AF: 0.0996

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.151

Alfa AF: 0.146 Hom.: 267

Bravo AF: 0.178

Asia WGS AF: 0.0740 AC: 261 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 08, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	4.2
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3020244; hg19: chr8-6263953;