8-6406286-T-C

Position:

• chr8-6406286-T-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.263A>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 0.685 in 421,574 control chromosomes in the GnomAD database, including 105,407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (31902 hom., cov: 33)
  • Exomes 𝑓: 0.73 (73505 hom.)
• Consequence: MCPH1-DT NR_040040.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.14

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=-0.88).
• BP6: Variant 8-6406286-T-C is Benign according to our data. Variant chr8-6406286-T-C is described in ClinVar as [Benign]. Clinvar id is 1277726.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.263A>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.287A>G		non_coding_transcript_exon_variant	1/2	2
MCPH1-DT	ENST00000523225.1	n.328A>G		non_coding_transcript_exon_variant	3/3	3
MCPH1-DT	ENST00000606853.2	n.295A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92381 AN: 151650 Hom.: 31904 Cov.: 33

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.815

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.625

GnomAD4 exome AF: 0.728 AC: 196387 AN: 269806 Hom.: 73505 Cov.: 0 AF XY: 0.730 AC XY: 100632 AN XY: 137872

Gnomad4 AFR exome AF: 0.303

Gnomad4 AMR exome AF: 0.563

Gnomad4 ASJ exome AF: 0.679

Gnomad4 EAS exome AF: 0.498

Gnomad4 SAS exome AF: 0.650

Gnomad4 FIN exome AF: 0.833

Gnomad4 NFE exome AF: 0.781

Gnomad4 OTH exome AF: 0.689

GnomAD4 genome AF: 0.609 AC: 92388 AN: 151768 Hom.: 31902 Cov.: 33 AF XY: 0.608 AC XY: 45073 AN XY: 74178

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.574

Gnomad4 ASJ AF: 0.680

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.617

Gnomad4 FIN AF: 0.815

Gnomad4 NFE AF: 0.786

Gnomad4 OTH AF: 0.625

Alfa AF: 0.715 Hom.: 8295

Bravo AF: 0.578

Asia WGS AF: 0.557 AC: 1935 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	-0.88
CADD	Benign	3.3
DANN	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2243674; hg19: chr8-6263807;