8-6406295-G-C

Position:

• chr8-6406295-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.254C>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 0.693 in 426,764 control chromosomes in the GnomAD database, including 108,095 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.62 (32623 hom., cov: 33)
  • Exomes 𝑓: 0.73 (75472 hom.)
• Consequence: MCPH1-DT NR_040040.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0470

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=-0.84).
• BP6: Variant 8-6406295-G-C is Benign according to our data. Variant chr8-6406295-G-C is described in ClinVar as [Benign]. Clinvar id is 1275193.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCPH1-DT	NR_040040.1	n.254C>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.278C>G		non_coding_transcript_exon_variant	1/2	2
MCPH1-DT	ENST00000523225.1	n.319C>G		non_coding_transcript_exon_variant	3/3	3
MCPH1-DT	ENST00000606853.2	n.286C>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94630 AN: 151690 Hom.: 32622 Cov.: 33

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.894

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.815

Gnomad MID AF: 0.640

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.636

GnomAD4 exome AF: 0.731 AC: 201099 AN: 274954 Hom.: 75472 Cov.: 0 AF XY: 0.733 AC XY: 103163 AN XY: 140752

Gnomad4 AFR exome AF: 0.356

Gnomad4 AMR exome AF: 0.570

Gnomad4 ASJ exome AF: 0.687

Gnomad4 EAS exome AF: 0.498

Gnomad4 SAS exome AF: 0.653

Gnomad4 FIN exome AF: 0.834

Gnomad4 NFE exome AF: 0.782

Gnomad4 OTH exome AF: 0.697

GnomAD4 genome AF: 0.624 AC: 94654 AN: 151810 Hom.: 32623 Cov.: 33 AF XY: 0.622 AC XY: 46166 AN XY: 74200

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.689

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.617

Gnomad4 FIN AF: 0.815

Gnomad4 NFE AF: 0.786

Gnomad4 OTH AF: 0.636

Alfa AF: 0.626 Hom.: 2430

Bravo AF: 0.595

Asia WGS AF: 0.564 AC: 1961 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	Jun 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
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: rs2243675; hg19: chr8-6263816;