chr1-147242742-C-T

Variant names:

• chr1-147242742-C-T
• rs1890042
• NM_004284.6:c.39C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004284.6(CHD1L):​c.39C>T​(p.Ala13Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 1,261,030 control chromosomes in the GnomAD database, including 34,446 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3541 hom., cov: 33)
  • Exomes 𝑓: 0.23 (30905 hom.)
• Consequence: CHD1L NM_004284.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.991
• Publications: 14 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]

FMO5 (HGNC:3773): (flavin containing dimethylaniline monoxygenase 5) Metabolic N-oxidation of the diet-derived amino-trimethylamine (TMA) is mediated by flavin-containing monooxygenase and is subject to an inherited FMO3 polymorphism in man resulting in a small subpopulation with reduced TMA N-oxidation capacity resulting in fish odor syndrome Trimethylaminuria. Three forms of the enzyme, FMO1 found in fetal liver, FMO2 found in adult liver, and FMO3 are encoded by genes clustered in the 1q23-q25 region. Flavin-containing monooxygenases are NADPH-dependent flavoenzymes that catalyzes the oxidation of soft nucleophilic heteroatom centers in drugs, pesticides, and xenobiotics. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2009]

FMO5 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000237188 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-147242742-C-T is Benign according to our data. Variant chr1-147242742-C-T is described in ClinVar as Benign. ClinVar VariationId is 1273099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.991 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.243 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.39C>T	p.Ala13Ala	synonymous	Exon 1 of 23	NP_004275.4
	CHD1L	NM_001348454.2		c.39C>T	p.Ala13Ala	synonymous	Exon 1 of 18	NP_001335383.1	A0A0A0MRH8
	CHD1L	NM_001256338.3		c.39C>T	p.Ala13Ala	synonymous	Exon 1 of 17	NP_001243267.1	Q86WJ1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD1L	ENST00000369258.8	TSL:1 MANE Select	c.39C>T	p.Ala13Ala	synonymous	Exon 1 of 23	ENSP00000358262.4	Q86WJ1-1
	CHD1L	ENST00000369259.4	TSL:1	c.39C>T	p.Ala13Ala	synonymous	Exon 1 of 17	ENSP00000358263.3	Q86WJ1-3
	CHD1L	ENST00000467213.5	TSL:1	n.39C>T		non_coding_transcript_exon	Exon 1 of 21	ENSP00000477985.1	A0A087WTM4

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31940 AN: 151946 Hom.: 3542 Cov.: 33

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.225

GnomAD4 exome AF: 0.233 AC: 258794 AN: 1108976 Hom.: 30905 Cov.: 35 AF XY: 0.234 AC XY: 123078 AN XY: 525584

African (AFR) AF: 0.145 AC: 3443 AN: 23808

American (AMR) AF: 0.221 AC: 2258 AN: 10198

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 2791 AN: 14478

East Asian (EAS) AF: 0.0864 AC: 2393 AN: 27686

South Asian (SAS) AF: 0.263 AC: 5473 AN: 20836

European-Finnish (FIN) AF: 0.249 AC: 8620 AN: 34664

Middle Eastern (MID) AF: 0.255 AC: 1004 AN: 3944

European-Non Finnish (NFE) AF: 0.240 AC: 222951 AN: 928924

Other (OTH) AF: 0.222 AC: 9861 AN: 44438

GnomAD4 genome AF: 0.210 AC: 31947 AN: 152054 Hom.: 3541 Cov.: 33 AF XY: 0.212 AC XY: 15740 AN XY: 74330

African (AFR) AF: 0.150 AC: 6213 AN: 41506

American (AMR) AF: 0.238 AC: 3636 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 657 AN: 3468

East Asian (EAS) AF: 0.107 AC: 549 AN: 5138

South Asian (SAS) AF: 0.255 AC: 1229 AN: 4818

European-Finnish (FIN) AF: 0.248 AC: 2626 AN: 10600

Middle Eastern (MID) AF: 0.272 AC: 79 AN: 290

European-Non Finnish (NFE) AF: 0.240 AC: 16267 AN: 67920

Other (OTH) AF: 0.224 AC: 473 AN: 2112

Alfa AF: 0.149 Hom.: 207

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	-0.79
CADD	Benign	5.8
PhyloP100		0.99
PromoterAI		0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs1890042; hg19: chr1-146714392;