rs1406712

Positions:

• chr15-92974463-T-C

Variant summary

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

The NM_001271.4(CHD2):​c.2506-416T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.078 in 152,296 control chromosomes in the GnomAD database, including 491 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 0.078 (491 hom., cov: 32)
• Consequence: CHD2 NM_001271.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.407

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 (SAS) allele frequency at 95% confidence interval = 0.0847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHD2	NM_001271.4	c.2506-416T>C		intron_variant		ENST00000394196.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHD2	ENST00000394196.9	c.2506-416T>C		intron_variant		5	NM_001271.4	P1

Frequencies

GnomAD3 genomes AF: 0.0781 AC: 11883 AN: 152178 Hom.: 491 Cov.: 32

Gnomad AFR AF: 0.0800

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0678

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.00461

Gnomad SAS AF: 0.0905

Gnomad FIN AF: 0.0453

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.0865

Gnomad OTH AF: 0.0974

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

GnomAD4 genome AF: 0.0780 AC: 11885 AN: 152296 Hom.: 491 Cov.: 32 AF XY: 0.0765 AC XY: 5695 AN XY: 74466

Gnomad4 AFR AF: 0.0799

Gnomad4 AMR AF: 0.0677

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.00462

Gnomad4 SAS AF: 0.0910

Gnomad4 FIN AF: 0.0453

Gnomad4 NFE AF: 0.0865

Gnomad4 OTH AF: 0.0964

Alfa AF: 0.0778 Hom.: 92

Bravo AF: 0.0796

Asia WGS AF: 0.0600 AC: 209 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	3.4
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1406712; hg19: chr15-93517693;