rs3763591

Variant names:

• chr8-60851830-G-T
• rs3763591
• NM_017780.4:c.5666-189G>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017780.4(CHD7):​c.5666-189G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 151,988 control chromosomes in the GnomAD database, including 30,300 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.62 (30300 hom., cov: 32)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.205

Genes affected

CHD7 (HGNC:20626): (chromodomain helicase DNA binding protein 7) This gene encodes a protein that contains several helicase family domains. Mutations in this gene have been found in some patients with the CHARGE syndrome. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 8-60851830-G-T is Benign according to our data. Variant chr8-60851830-G-T is described in ClinVar as [Benign]. Clinvar id is 676812.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD7	NM_017780.4	c.5666-189G>T		intron_variant	Intron 28 of 37	ENST00000423902.7	NP_060250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD7	ENST00000423902.7	c.5666-189G>T		intron_variant	Intron 28 of 37	5	NM_017780.4	ENSP00000392028.1
CHD7	ENST00000524602.5	c.1717-10399G>T		intron_variant	Intron 2 of 4	1		ENSP00000437061.1
CHD7	ENST00000527921.1	n.157-189G>T		intron_variant	Intron 3 of 4	4
CHD7	ENST00000695853.1	n.5666-189G>T		intron_variant	Intron 28 of 36			ENSP00000512218.1

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94859 AN: 151870 Hom.: 30273 Cov.: 32

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.578

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

GnomAD4 genome AF: 0.625 AC: 94943 AN: 151988 Hom.: 30300 Cov.: 32 AF XY: 0.633 AC XY: 47043 AN XY: 74290

Gnomad4 AFR AF: 0.732

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.759

Gnomad4 SAS AF: 0.733

Gnomad4 FIN AF: 0.631

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.580

Alfa AF: 0.599 Hom.: 4105

Bravo AF: 0.621

Asia WGS AF: 0.702 AC: 2437 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.66
DANN	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs3763591; hg19: chr8-61764389;