rs6503966

Variant names:

• chr17-60425499-C-T
• rs6503966
• NM_181707.3:c.52-284C>T

Variant summary

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

The NM_181707.3(CHCT1):​c.52-284C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,104 control chromosomes in the GnomAD database, including 8,820 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 0.22 (8820 hom., cov: 32)
• Consequence: CHCT1 NM_181707.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.143
• Publications: 3 publications found

Genes affected

CHCT1 (HGNC:26990): (CHD1 helical C-terminal domain containing 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHCT1	NM_181707.3	c.52-284C>T		intron_variant	Intron 1 of 5	ENST00000269127.5	NP_859058.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHCT1	ENST00000269127.5	c.52-284C>T		intron_variant	Intron 1 of 5	1	NM_181707.3	ENSP00000269127.4
CHCT1	ENST00000474834.5	c.-60-284C>T		intron_variant	Intron 1 of 3	3		ENSP00000467637.1
CHCT1	ENST00000461535.1	c.-60-284C>T		intron_variant	Intron 1 of 1	2		ENSP00000468617.1
CHCT1	ENST00000464714.1	n.110-284C>T		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32772 AN: 151986 Hom.: 8780 Cov.: 32

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.0489

Gnomad SAS AF: 0.0754

Gnomad FIN AF: 0.0363

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0400

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.216 AC: 32861 AN: 152104 Hom.: 8820 Cov.: 32 AF XY: 0.211 AC XY: 15655 AN XY: 74364

African (AFR) AF: 0.635 AC: 26324 AN: 41426

American (AMR) AF: 0.147 AC: 2246 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0467 AC: 162 AN: 3472

East Asian (EAS) AF: 0.0488 AC: 253 AN: 5180

South Asian (SAS) AF: 0.0746 AC: 360 AN: 4826

European-Finnish (FIN) AF: 0.0363 AC: 384 AN: 10580

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.0399 AC: 2716 AN: 68024

Other (OTH) AF: 0.173 AC: 367 AN: 2116

Alfa AF: 0.0871 Hom.: 1266

Bravo AF: 0.244

Asia WGS AF: 0.106 AC: 368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.7
DANN	Benign	0.37
PhyloP100		-0.14
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: rs6503966; hg19: chr17-58502860;