15-92918141-C-G

Position:

• chr15-92918141-C-G

Variant summary

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

The NM_001271.4(CHD2):​c.63-6180C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 152,036 control chromosomes in the GnomAD database, including 25,195 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 0.57 (25195 hom., cov: 32)
• Consequence: CHD2 NM_001271.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.421

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD2	NM_001271.4	c.63-6180C>G		intron_variant		ENST00000394196.9	NP_001262.3
CHD2	NM_001042572.3	c.63-6180C>G		intron_variant			NP_001036037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHD2	ENST00000394196.9	c.63-6180C>G		intron_variant		5	NM_001271.4	ENSP00000377747	P1

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86344 AN: 151918 Hom.: 25164 Cov.: 32

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.857

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.568

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

GnomAD4 genome AF: 0.568 AC: 86425 AN: 152036 Hom.: 25195 Cov.: 32 AF XY: 0.576 AC XY: 42809 AN XY: 74328

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.661

Gnomad4 ASJ AF: 0.624

Gnomad4 EAS AF: 0.857

Gnomad4 SAS AF: 0.733

Gnomad4 FIN AF: 0.619

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.570

Alfa AF: 0.434 Hom.: 1198

Bravo AF: 0.568

Asia WGS AF: 0.767 AC: 2665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.43

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: rs1406714; hg19: chr15-93461371;