NM_004284.6:c.128-337C>T

Variant names:

• chr1-147252286-C-T
• rs1890038
• NM_004284.6:c.128-337C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.373
• Publications: 6 publications found

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

ENSG00000237188 (HGNC:):

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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.: 32

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.: 32 AF XY: 0.161 AC XY: 11978 AN XY: 74378

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: 54 AN: 294

European-Non Finnish (NFE) AF: 0.0727 AC: 4945 AN: 68010

Other (OTH) AF: 0.155 AC: 327 AN: 2114

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

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.88
DANN	Benign	0.19
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1890038; hg19: chr1-146723941; COSMIC: COSV63614074;