8-6406391-A-T

Position:

• chr8-6406391-A-T

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.158T>A 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 0.0935 in 512,142 control chromosomes in the GnomAD database, including 3,146 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1715 hom., cov: 34)
  • Exomes 𝑓: 0.080 (1431 hom.)
• Consequence: MCPH1-DT NR_040040.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.721

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=-0.82).
• BP6: Variant 8-6406391-A-T is Benign according to our data. Variant chr8-6406391-A-T is described in ClinVar as [Benign]. Clinvar id is 1243287.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCPH1-DT	NR_040040.1	n.158T>A		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCPH1-DT	ENST00000500118.4	n.182T>A		non_coding_transcript_exon_variant	1/2	2
MCPH1-DT	ENST00000606853.2	n.190T>A		non_coding_transcript_exon_variant	1/1
MCPH1-DT	ENST00000523225.1	n.243-20T>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19172 AN: 152070 Hom.: 1707 Cov.: 34

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.0713

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0151

Gnomad SAS AF: 0.0640

Gnomad FIN AF: 0.0638

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.0839

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.0796 AC: 28663 AN: 359954 Hom.: 1431 Cov.: 0 AF XY: 0.0792 AC XY: 14917 AN XY: 188400

Gnomad4 AFR exome AF: 0.244

Gnomad4 AMR exome AF: 0.0598

Gnomad4 ASJ exome AF: 0.147

Gnomad4 EAS exome AF: 0.00502

Gnomad4 SAS exome AF: 0.0611

Gnomad4 FIN exome AF: 0.0568

Gnomad4 NFE exome AF: 0.0831

Gnomad4 OTH exome AF: 0.0978

GnomAD4 genome AF: 0.126 AC: 19199 AN: 152188 Hom.: 1715 Cov.: 34 AF XY: 0.122 AC XY: 9110 AN XY: 74424

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.0712

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.0149

Gnomad4 SAS AF: 0.0647

Gnomad4 FIN AF: 0.0638

Gnomad4 NFE AF: 0.0838

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0366 Hom.: 32

Bravo AF: 0.133

Asia WGS AF: 0.0590 AC: 208 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	Jul 08, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2916656; hg19: chr8-6263912;