8-6406364-C-G

Position:

• chr8-6406364-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.185G>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 0.00449 in 494,966 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (5 hom., cov: 34)
  • Exomes 𝑓: 0.0048 (10 hom.)
• Consequence: MCPH1-DT NR_040040.1 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0710

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 8-6406364-C-G is Benign according to our data. Variant chr8-6406364-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1212188.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCPH1-DT	NR_040040.1	n.185G>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.209G>C		non_coding_transcript_exon_variant	1/2	2
MCPH1-DT	ENST00000523225.1	n.250G>C		non_coding_transcript_exon_variant	3/3	3
MCPH1-DT	ENST00000606853.2	n.217G>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.00384 AC: 585 AN: 152178 Hom.: 5 Cov.: 34

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00819

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00645

Gnomad OTH AF: 0.000956

GnomAD4 exome AF: 0.00477 AC: 1636 AN: 342670 Hom.: 10 Cov.: 0 AF XY: 0.00456 AC XY: 814 AN XY: 178558

Gnomad4 AFR exome AF: 0.00121

Gnomad4 AMR exome AF: 0.000490

Gnomad4 ASJ exome AF: 0.00184

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00115

Gnomad4 FIN exome AF: 0.00852

Gnomad4 NFE exome AF: 0.00585

Gnomad4 OTH exome AF: 0.00366

GnomAD4 genome AF: 0.00384 AC: 585 AN: 152296 Hom.: 5 Cov.: 34 AF XY: 0.00381 AC XY: 284 AN XY: 74480

Gnomad4 AFR AF: 0.00101

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00819

Gnomad4 NFE AF: 0.00645

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.0112 Hom.: 4

Bravo AF: 0.00272

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

Mar 08, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.5
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs576392182; hg19: chr8-6263885;