Genetic Variant MCPH1-DT:n.295A>G (chr8-6406286-T-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.295A>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 0.685 in 421,574 control chromosomes in the GnomAD database, including 105,407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.61 ( 31902 hom., cov: 33)

Exomes 𝑓: 0.73 ( 73505 hom. )

Consequence

MCPH1-DT
ENST00000500118.5 non_coding_transcript_exon

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.14

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=-0.88).

BP6

Variant 8-6406286-T-C is Benign according to our data. Variant chr8-6406286-T-C is described in ClinVar as [Benign]. Clinvar id is 1277726.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.263A>G		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
MCPH1-DT	ENST00000500118.5 link	n.295A>G	non_coding_transcript_exon_variant	Exon 1 of 2	2
MCPH1-DT	ENST00000523225.2 link	n.328A>G	non_coding_transcript_exon_variant	Exon 3 of 3	3
MCPH1-DT	ENST00000606853.3 link	n.313A>G	non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

AF:

0.609

AC:

92381

AN:

151650

Hom.:

31904

Cov.:

show subpopulations

Gnomad AFR

AF:

0.283

Gnomad AMI

AF:

0.895

Gnomad AMR

AF:

0.574

Gnomad ASJ

AF:

0.680

Gnomad EAS

AF:

0.475

Gnomad SAS

AF:

0.618

Gnomad FIN

AF:

0.815

Gnomad MID

AF:

0.615

Gnomad NFE

AF:

0.786

Gnomad OTH

AF:

0.625

GnomAD4 exome

AF:

0.728

AC:

196387

AN:

269806

Hom.:

73505

Cov.:

AF XY:

0.730

AC XY:

100632

AN XY:

137872

show subpopulations

African (AFR)

AF:

0.303

AC:

2174

AN:

7166

American (AMR)

AF:

0.563

AC:

4608

AN:

8188

Ashkenazi Jewish (ASJ)

AF:

0.679

AC:

6502

AN:

9578

East Asian (EAS)

AF:

0.498

AC:

11378

AN:

22868

South Asian (SAS)

AF:

0.650

AC:

4939

AN:

7596

European-Finnish (FIN)

AF:

0.833

AC:

18555

AN:

22280

Middle Eastern (MID)

AF:

0.665

AC:

907

AN:

1364

European-Non Finnish (NFE)

AF:

0.781

AC:

135164

AN:

173126

Other (OTH)

AF:

0.689

AC:

12160

AN:

17640

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

2375

4750

7126

9501

11876

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.609

AC:

92388

AN:

151768

Hom.:

31902

Cov.:

AF XY:

0.608

AC XY:

45073

AN XY:

74178

show subpopulations

African (AFR)

AF:

0.282

AC:

11695

AN:

41446

American (AMR)

AF:

0.574

AC:

8753

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.680

AC:

2354

AN:

3462

East Asian (EAS)

AF:

0.474

AC:

2430

AN:

5122

South Asian (SAS)

AF:

0.617

AC:

2974

AN:

4818

European-Finnish (FIN)

AF:

0.815

AC:

8596

AN:

10542

Middle Eastern (MID)

AF:

0.599

AC:

176

AN:

294

European-Non Finnish (NFE)

AF:

0.786

AC:

53287

AN:

67818

Other (OTH)

AF:

0.625

AC:

1316

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1507

3015

4522

6030

7537

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.715

Hom.:

8295

Bravo

AF:

0.578

Asia WGS

AF:

0.557

AC:

1935

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

-0.88

CADD

Benign

3.3

(source)

DANN

Benign

0.32

PhyloP100

-3.1

PromoterAI

-0.0034

Neutral

(source)

Splicing

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

Publications

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8-6406286-T-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