chr1-147252348-A-G

Position:

• chr1-147252348-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004284.6(CHD1L):​c.128-275A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0937 in 152,260 control chromosomes in the GnomAD database, including 741 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.094 (741 hom., cov: 32)
• Consequence: CHD1L NM_004284.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.189

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]

ENSG00000237188 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-147252348-A-G is Benign according to our data. Variant chr1-147252348-A-G is described in ClinVar as [Benign]. Clinvar id is 1229631.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD1L	NM_004284.6	c.128-275A>G		intron_variant		ENST00000369258.8	NP_004275.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHD1L	ENST00000369258.8	c.128-275A>G		intron_variant		1	NM_004284.6	ENSP00000358262.4

Frequencies

GnomAD3 genomes AF: 0.0937 AC: 14258 AN: 152142 Hom.: 736 Cov.: 32

Gnomad AFR AF: 0.0790

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0582

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0885

Gnomad OTH AF: 0.0876

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

GnomAD4 genome AF: 0.0937 AC: 14271 AN: 152260 Hom.: 741 Cov.: 32 AF XY: 0.0961 AC XY: 7157 AN XY: 74450

Gnomad4 AFR AF: 0.0789

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.0582

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.0885

Gnomad4 OTH AF: 0.0885

Alfa AF: 0.0943 Hom.: 114

Bravo AF: 0.0911

Asia WGS AF: 0.139 AC: 482 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.4
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3820130; hg19: chr1-146724003; COSMIC: COSV63613226;