8-6406319-C-G

Position:

• chr8-6406319-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NR_040040.1(MCPH1-DT):​n.230G>C 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 0.00948 in 450,692 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0084 (6 hom., cov: 34)
  • Exomes 𝑓: 0.010 (29 hom.)
• Consequence: MCPH1-DT NR_040040.1 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0780

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 8-6406319-C-G is Benign according to our data. Variant chr8-6406319-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1202967.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCPH1-DT	NR_040040.1	n.230G>C		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCPH1-DT	ENST00000500118.4	n.254G>C		non_coding_transcript_exon_variant	1/2	2
MCPH1-DT	ENST00000523225.1	n.295G>C		non_coding_transcript_exon_variant	3/3	3
MCPH1-DT	ENST00000606853.2	n.262G>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.00846 AC: 1287 AN: 152210 Hom.: 6 Cov.: 34

Gnomad AFR AF: 0.00234

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.00961

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00405

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0139

Gnomad OTH AF: 0.00814

GnomAD4 exome AF: 0.0100 AC: 2988 AN: 298364 Hom.: 29 Cov.: 0 AF XY: 0.00983 AC XY: 1509 AN XY: 153534

Gnomad4 AFR exome AF: 0.00208

Gnomad4 AMR exome AF: 0.00868

Gnomad4 ASJ exome AF: 0.000894

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00237

Gnomad4 FIN exome AF: 0.00525

Gnomad4 NFE exome AF: 0.0134

Gnomad4 OTH exome AF: 0.00899

GnomAD4 genome AF: 0.00844 AC: 1286 AN: 152328 Hom.: 6 Cov.: 34 AF XY: 0.00753 AC XY: 561 AN XY: 74480

Gnomad4 AFR AF: 0.00233

Gnomad4 AMR AF: 0.00960

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00405

Gnomad4 NFE AF: 0.0139

Gnomad4 OTH AF: 0.00806

Alfa AF: 0.0102 Hom.: 2

Bravo AF: 0.00870

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.7
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs41302212; hg19: chr8-6263840;