8-6406319-C-G

Variant names:

• chr8-6406319-C-G
• rs41302212
• ENST00000500118.5:n.262G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000500118.5(MCPH1-DT):​n.262G>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 0.00948 in 450,692 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0084 (6 hom., cov: 34)
  • Exomes 𝑓: 0.010 (29 hom.)
• Consequence: MCPH1-DT ENST00000500118.5 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0780
• Publications: 2 publications found

Genes affected

MCPH1-DT (HGNC:55599): (MCPH1 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 8-6406319-C-G is Benign according to our data. Variant chr8-6406319-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1202967.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCPH1-DT	NR_040040.1	n.230G>C		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCPH1-DT	ENST00000500118.5	n.262G>C		non_coding_transcript_exon_variant	Exon 1 of 2	2
MCPH1-DT	ENST00000523225.2	n.295G>C		non_coding_transcript_exon_variant	Exon 3 of 3	3
MCPH1-DT	ENST00000606853.3	n.280G>C		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.00846 AC: 1287 AN: 152210 Hom.: 6 Cov.: 34

Gnomad AFR AF: 0.00234

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.00961

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00405

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0139

Gnomad OTH AF: 0.00814

GnomAD4 exome AF: 0.0100 AC: 2988 AN: 298364 Hom.: 29 Cov.: 0 AF XY: 0.00983 AC XY: 1509 AN XY: 153534

African (AFR) AF: 0.00208 AC: 15 AN: 7214

American (AMR) AF: 0.00868 AC: 77 AN: 8876

Ashkenazi Jewish (ASJ) AF: 0.000894 AC: 9 AN: 10066

East Asian (EAS) AF: 0.00 AC: 0 AN: 23406

South Asian (SAS) AF: 0.00237 AC: 33 AN: 13946

European-Finnish (FIN) AF: 0.00525 AC: 128 AN: 24400

Middle Eastern (MID) AF: 0.00138 AC: 2 AN: 1454

European-Non Finnish (NFE) AF: 0.0134 AC: 2553 AN: 189978

Other (OTH) AF: 0.00899 AC: 171 AN: 19024

GnomAD4 genome AF: 0.00844 AC: 1286 AN: 152328 Hom.: 6 Cov.: 34 AF XY: 0.00753 AC XY: 561 AN XY: 74480

African (AFR) AF: 0.00233 AC: 97 AN: 41570

American (AMR) AF: 0.00960 AC: 147 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4824

European-Finnish (FIN) AF: 0.00405 AC: 43 AN: 10626

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0139 AC: 943 AN: 68032

Other (OTH) AF: 0.00806 AC: 17 AN: 2110

Alfa AF: 0.0102 Hom.: 2

Bravo AF: 0.00870

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 22, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.7
DANN	Benign	0.48
PhyloP100		0.078
PromoterAI		-0.13	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs41302212; hg19: chr8-6263840;