rs7179432

Positions:

• chr15-93021742-T-C
• chr15-93021742-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000626874.2(CHD2):​c.*1417T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 152,016 control chromosomes in the GnomAD database, including 16,681 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 0.45 (16680 hom., cov: 32)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: CHD2 ENST00000626874.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.295

Genes affected

CHD2 (HGNC:1917): (chromodomain helicase DNA binding protein 2) The CHD family of proteins is characterized by the presence of chromo (chromatin organization modifier) domains and SNF2-related helicase/ATPase domains. CHD genes alter gene expression possibly by modification of chromatin structure thus altering access of the transcriptional apparatus to its chromosomal DNA template. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD2	NM_001271.4	c.5153+1484T>C		intron_variant		ENST00000394196.9	NP_001262.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHD2	ENST00000626874.2	c.*1417T>C		3_prime_UTR_variant	38/38	1		ENSP00000486629
CHD2	ENST00000394196.9	c.5153+1484T>C		intron_variant		5	NM_001271.4	ENSP00000377747	P1
CHD2	ENST00000625662.3	c.*1324+1484T>C		intron_variant, NMD_transcript_variant		5		ENSP00000486007
CHD2	ENST00000627460.1	c.*285+1484T>C		intron_variant, NMD_transcript_variant		5		ENSP00000485982

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68558 AN: 151896 Hom.: 16666 Cov.: 32

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.896

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.441

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.451 AC: 68594 AN: 152014 Hom.: 16680 Cov.: 32 AF XY: 0.462 AC XY: 34345 AN XY: 74292

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.512

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.896

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.602

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.448

Alfa AF: 0.449 Hom.: 21637

Bravo AF: 0.437

Asia WGS AF: 0.700 AC: 2434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.1
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7179432; hg19: chr15-93564972;