rs3763591

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

CHD7 Gene-Disease associations (from GenCC):

• CHARGE syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), Broad Center for Mendelian Genomics, ClinGen
• hypogonadotropic hypogonadism 5 with or without anosmia

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• hypogonadotropic hypogonadism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Kallmann syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Omenn syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017780.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD7	NM_017780.4	MANE Select	c.5666-189G>T		intron	N/A	NP_060250.2
	CHD7	NM_001316690.1		c.1717-10399G>T		intron	N/A	NP_001303619.1	Q9P2D1-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD7	ENST00000423902.7	TSL:5 MANE Select	c.5666-189G>T		intron	N/A	ENSP00000392028.1	Q9P2D1-1
	CHD7	ENST00000524602.5	TSL:1	c.1717-10399G>T		intron	N/A	ENSP00000437061.1	Q9P2D1-4
	CHD7	ENST00000933299.1		c.5702-189G>T		intron	N/A	ENSP00000603358.1

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

African (AFR) AF: 0.732 AC: 30329 AN: 41408

American (AMR) AF: 0.613 AC: 9372 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1852 AN: 3470

East Asian (EAS) AF: 0.759 AC: 3929 AN: 5178

South Asian (SAS) AF: 0.733 AC: 3533 AN: 4820

European-Finnish (FIN) AF: 0.631 AC: 6652 AN: 10548

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.551 AC: 37453 AN: 67966

Other (OTH) AF: 0.580 AC: 1223 AN: 2110

Alfa AF: 0.599 Hom.: 4105

Bravo AF: 0.621

Asia WGS AF: 0.702 AC: 2437 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.66
DANN	Benign	0.38
PhyloP100		-0.20
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: rs3763591; hg19: chr8-61764389;