Genetic Variant CHD1L:c.128-337C>T (chr1-147252286-C-T) – 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 NM_004284.6(CHD1L):c.128-337C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,142 control chromosomes in the GnomAD database, including 2,553 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2553 hom., cov: 32)

Consequence

CHD1L
NM_004284.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.373

Publications

6 publications found

Variant links:

Genes affected

CHD1L (HGNC:1916): (chromodomain helicase DNA binding protein 1 like) This gene encodes a DNA helicase protein involved in DNA repair. The protein converts ATP to add poly(ADP-ribose) as it regulates chromatin relaxation following DNA damage. Overexpression of this gene has been linked to several types of cancers. [provided by RefSeq, Feb 2017]

CHD1L Gene-Disease associations (from GenCC):

congenital anomaly of kidney and urinary tract
Inheritance: Unknown Classification: LIMITED Submitted by: ClinGen

CHD1L links:

ENSG00000237188 (HGNC:):

ENSG00000237188 links:

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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=-0.87).

BP6

Variant 1-147252286-C-T is Benign according to our data. Variant chr1-147252286-C-T is described in ClinVar as Benign. ClinVar VariationId is 1268291.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004284.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHD1L	NM_004284.6	MANE Select	c.128-337C>T	intron	N/A	NP_004275.4
CHD1L	NM_001348451.2		c.-89-337C>T	intron	N/A	NP_001335380.1	A0A0A0MSH9
CHD1L	NM_001348452.2		c.-89-337C>T	intron	N/A	NP_001335381.1	A0A0A0MSH9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHD1L	ENST00000369258.8	TSL:1 MANE Select	c.128-337C>T	intron	N/A	ENSP00000358262.4	Q86WJ1-1
CHD1L	ENST00000369259.4	TSL:1	c.127+9456C>T	intron	N/A	ENSP00000358263.3	Q86WJ1-3
CHD1L	ENST00000467213.5	TSL:1	n.128-337C>T	intron	N/A	ENSP00000477985.1	A0A087WTM4

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23690

AN:

152024

Hom.:

2540

Cov.:

show subpopulations

Gnomad AFR

AF:

0.253

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.437

Gnomad SAS

AF:

0.235

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.0727

Gnomad OTH

AF:

0.150

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.156

AC:

23744

AN:

152142

Hom.:

2553

Cov.:

AF XY:

0.161

AC XY:

11978

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.254

AC:

10519

AN:

41488

American (AMR)

AF:

0.176

AC:

2691

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.132

AC:

457

AN:

3468

East Asian (EAS)

AF:

0.437

AC:

2251

AN:

5150

South Asian (SAS)

AF:

0.236

AC:

1137

AN:

4826

European-Finnish (FIN)

AF:

0.116

AC:

1225

AN:

10596

Middle Eastern (MID)

AF:

0.184

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0727

AC:

4945

AN:

68010

Other (OTH)

AF:

0.155

AC:

327

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

978

1957

2935

3914

4892

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

270

540

810

1080

1350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.112

Hom.:

513

Bravo

AF:

0.167

Asia WGS

AF:

0.310

AC:

1077

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.88

(source)

DANN

Benign

0.19

PhyloP100

-0.37

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over