8-6406522-C-T

Position:

• chr8-6406522-C-T

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.27G>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 0.00103 in 854,686 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0032 (4 hom., cov: 34)
  • Exomes 𝑓: 0.00057 (0 hom.)
• Consequence: MCPH1-DT NR_040040.1 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.432

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=-0.73).
• BP6: Variant 8-6406522-C-T is Benign according to our data. Variant chr8-6406522-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1179530.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCPH1-DT	NR_040040.1	n.27G>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.51G>A		non_coding_transcript_exon_variant	1/2	2
MCPH1-DT	ENST00000606853.2	n.59G>A		non_coding_transcript_exon_variant	1/1
MCPH1-DT	ENST00000523225.1	n.242+6G>A		splice_donor_region_variant, intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00311 AC: 474 AN: 152204 Hom.: 2 Cov.: 34

Gnomad AFR AF: 0.00994

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.000570 AC: 400 AN: 702364 Hom.: 0 Cov.: 9 AF XY: 0.000529 AC XY: 190 AN XY: 359062

Gnomad4 AFR exome AF: 0.0125

Gnomad4 AMR exome AF: 0.000839

Gnomad4 ASJ exome AF: 0.00761

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000593

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000614

Gnomad4 OTH exome AF: 0.00148

GnomAD4 genome AF: 0.00318 AC: 484 AN: 152322 Hom.: 4 Cov.: 34 AF XY: 0.00317 AC XY: 236 AN XY: 74486

Gnomad4 AFR AF: 0.0102

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00284

Bravo AF: 0.00390

Asia WGS AF: 0.00231 AC: 8 AN: 3478

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

Jan 06, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	4.8
DANN	Benign	0.77
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: rs140279025; hg19: chr8-6264043;