Genetic Variant MCPH1-DT:n.286C>G (chr8-6406295-G-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000500118.5(MCPH1-DT):n.286C>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 0.693 in 426,764 control chromosomes in the GnomAD database, including 108,095 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 32623 hom., cov: 33)

Exomes 𝑓: 0.73 ( 75472 hom. )

Consequence

MCPH1-DT
ENST00000500118.5 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0470

Publications

2 publications found

Variant links:

Genes affected

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

MCPH1-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 8-6406295-G-C is Benign according to our data. Variant chr8-6406295-G-C is described in ClinVar as [Benign]. Clinvar id is 1275193.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 rank	MANE	Protein	UniProt
MCPH1-DT	NR_040040.1 link	n.254C>G		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
MCPH1-DT	ENST00000500118.5 link	n.286C>G	non_coding_transcript_exon_variant	Exon 1 of 2	2
MCPH1-DT	ENST00000523225.2 link	n.319C>G	non_coding_transcript_exon_variant	Exon 3 of 3	3
MCPH1-DT	ENST00000606853.3 link	n.304C>G	non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

AF:

0.624

AC:

94630

AN:

151690

Hom.:

32622

Cov.:

show subpopulations

Gnomad AFR

AF:

0.333

Gnomad AMI

AF:

0.894

Gnomad AMR

AF:

0.578

Gnomad ASJ

AF:

0.689

Gnomad EAS

AF:

0.476

Gnomad SAS

AF:

0.617

Gnomad FIN

AF:

0.815

Gnomad MID

AF:

0.640

Gnomad NFE

AF:

0.786

Gnomad OTH

AF:

0.636

GnomAD4 exome

AF:

0.731

AC:

201099

AN:

274954

Hom.:

75472

Cov.:

AF XY:

0.733

AC XY:

103163

AN XY:

140752

show subpopulations

African (AFR)

AF:

0.356

AC:

2548

AN:

7150

American (AMR)

AF:

0.570

AC:

4721

AN:

8286

Ashkenazi Jewish (ASJ)

AF:

0.687

AC:

6635

AN:

9664

East Asian (EAS)

AF:

0.498

AC:

11448

AN:

22974

South Asian (SAS)

AF:

0.653

AC:

5730

AN:

8774

European-Finnish (FIN)

AF:

0.834

AC:

18891

AN:

22654

Middle Eastern (MID)

AF:

0.673

AC:

931

AN:

1384

European-Non Finnish (NFE)

AF:

0.782

AC:

137741

AN:

176202

Other (OTH)

AF:

0.697

AC:

12454

AN:

17866

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

2435

4869

7304

9738

12173

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.624

AC:

94654

AN:

151810

Hom.:

32623

Cov.:

AF XY:

0.622

AC XY:

46166

AN XY:

74200

show subpopulations

African (AFR)

AF:

0.333

AC:

13799

AN:

41450

American (AMR)

AF:

0.578

AC:

8824

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.689

AC:

2386

AN:

3462

East Asian (EAS)

AF:

0.475

AC:

2443

AN:

5140

South Asian (SAS)

AF:

0.617

AC:

2970

AN:

4816

European-Finnish (FIN)

AF:

0.815

AC:

8596

AN:

10542

Middle Eastern (MID)

AF:

0.626

AC:

184

AN:

294

European-Non Finnish (NFE)

AF:

0.786

AC:

53305

AN:

67832

Other (OTH)

AF:

0.636

AC:

1342

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1574

3149

4723

6298

7872

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.626

Hom.:

2430

Bravo

AF:

0.595

Asia WGS

AF:

0.564

AC:

1961

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 16, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.4

(source)

DANN

Benign

0.48

PhyloP100

0.047

PromoterAI

0.016

Neutral

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

8-6406295-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over