8-6406426-C-G

Position:

• chr8-6406426-C-G

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.123G>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 0.674 in 549,296 control chromosomes in the GnomAD database, including 131,408 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (30102 hom., cov: 33)
  • Exomes 𝑓: 0.71 (101306 hom.)
• Consequence: MCPH1-DT NR_040040.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.969

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=-0.75).
• BP6: Variant 8-6406426-C-G is Benign according to our data. Variant chr8-6406426-C-G is described in ClinVar as [Benign]. Clinvar id is 1245106.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCPH1-DT	NR_040040.1	n.123G>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.147G>C		non_coding_transcript_exon_variant	1/2	2
MCPH1-DT	ENST00000606853.2	n.155G>C		non_coding_transcript_exon_variant	1/1
MCPH1-DT	ENST00000523225.1	n.243-55G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89833 AN: 151720 Hom.: 30106 Cov.: 33

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.613

GnomAD4 exome AF: 0.706 AC: 280423 AN: 397460 Hom.: 101306 Cov.: 3 AF XY: 0.702 AC XY: 147153 AN XY: 209520

Gnomad4 AFR exome AF: 0.292

Gnomad4 AMR exome AF: 0.552

Gnomad4 ASJ exome AF: 0.666

Gnomad4 EAS exome AF: 0.493

Gnomad4 SAS exome AF: 0.615

Gnomad4 FIN exome AF: 0.800

Gnomad4 NFE exome AF: 0.759

Gnomad4 OTH exome AF: 0.677

GnomAD4 genome AF: 0.592 AC: 89837 AN: 151836 Hom.: 30102 Cov.: 33 AF XY: 0.590 AC XY: 43795 AN XY: 74214

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.564

Gnomad4 ASJ AF: 0.669

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.611

Gnomad4 FIN AF: 0.779

Gnomad4 NFE AF: 0.764

Gnomad4 OTH AF: 0.614

Alfa AF: 0.668 Hom.: 4541

Bravo AF: 0.562

Asia WGS AF: 0.553 AC: 1922 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	clinical testing	GeneDx	Jun 16, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	2.7
DANN	Benign	0.46
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: rs2243756; hg19: chr8-6263947;