rs2077749

Variant names:

• chr1-147181057-G-A
• rs2077749
• NM_001348451.2:c.-90+6472G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001348451.2(CHD1L):​c.-90+6472G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 152,052 control chromosomes in the GnomAD database, including 10,989 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (10989 hom., cov: 32)
• Consequence: CHD1L NM_001348451.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD1L	NM_001348451.2	c.-90+6472G>A		intron_variant	Intron 2 of 23		NP_001335380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMO5	ENST00000527849.5	n.*259-4667C>T		intron_variant	Intron 8 of 8	5		ENSP00000433742.1
ENSG00000237188	ENST00000606757.1	n.258+6472G>A		intron_variant	Intron 2 of 2	3
ENSG00000237188	ENST00000606856.1	n.536+6472G>A		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56638 AN: 151930 Hom.: 10972 Cov.: 32

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.373 AC: 56691 AN: 152052 Hom.: 10989 Cov.: 32 AF XY: 0.372 AC XY: 27666 AN XY: 74306

African (AFR) AF: 0.496 AC: 20570 AN: 41462

American (AMR) AF: 0.339 AC: 5189 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1035 AN: 3470

East Asian (EAS) AF: 0.297 AC: 1535 AN: 5160

South Asian (SAS) AF: 0.401 AC: 1930 AN: 4816

European-Finnish (FIN) AF: 0.323 AC: 3405 AN: 10546

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21915 AN: 67994

Other (OTH) AF: 0.353 AC: 745 AN: 2110

Alfa AF: 0.339 Hom.: 12694

Bravo AF: 0.374

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.8
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs2077749; hg19: chr1-146652637;