rs7836586

Variant names:

• chr8-60743131-G-A
• rs7836586
• NM_017780.4:c.1665+34G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-60743131-G-A
• chr8-60743131-G-C

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.1665+34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 1,565,432 control chromosomes in the GnomAD database, including 471,415 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (45876 hom., cov: 33)
  • Exomes 𝑓: 0.77 (425539 hom.)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.0130
• Publications: 13 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=-0.89).
• BP6: Variant 8-60743131-G-A is Benign according to our data. Variant chr8-60743131-G-A is described in ClinVar as Benign. ClinVar VariationId is 158324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.917 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.1665+34G>A		intron	N/A	NP_060250.2
	CHD7	NM_001316690.1		c.1665+34G>A		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.1665+34G>A		intron	N/A	ENSP00000392028.1	Q9P2D1-1
	CHD7	ENST00000524602.5	TSL:1	c.1665+34G>A		intron	N/A	ENSP00000437061.1	Q9P2D1-4
	CHD7	ENST00000933299.1		c.1665+34G>A		intron	N/A	ENSP00000603358.1

Frequencies

GnomAD3 genomes AF: 0.774 AC: 117740 AN: 152060 Hom.: 45855 Cov.: 33

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.759

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.911

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.763

GnomAD2 exomes AF: 0.809 AC: 181227 AN: 224094 AF XY: 0.812

Gnomad AFR exome AF: 0.743

Gnomad AMR exome AF: 0.819

Gnomad ASJ exome AF: 0.762

Gnomad EAS exome AF: 0.939

Gnomad FIN exome AF: 0.836

Gnomad NFE exome AF: 0.765

Gnomad OTH exome AF: 0.777

GnomAD4 exome AF: 0.774 AC: 1093849 AN: 1413254 Hom.: 425539 Cov.: 24 AF XY: 0.778 AC XY: 547502 AN XY: 703826

African (AFR) AF: 0.731 AC: 23635 AN: 32316

American (AMR) AF: 0.815 AC: 34715 AN: 42584

Ashkenazi Jewish (ASJ) AF: 0.764 AC: 19563 AN: 25612

East Asian (EAS) AF: 0.948 AC: 36762 AN: 38760

South Asian (SAS) AF: 0.910 AC: 75802 AN: 83326

European-Finnish (FIN) AF: 0.833 AC: 42005 AN: 50446

Middle Eastern (MID) AF: 0.738 AC: 4204 AN: 5700

European-Non Finnish (NFE) AF: 0.754 AC: 811182 AN: 1075726

Other (OTH) AF: 0.782 AC: 45981 AN: 58784

GnomAD4 genome AF: 0.774 AC: 117808 AN: 152178 Hom.: 45876 Cov.: 33 AF XY: 0.782 AC XY: 58213 AN XY: 74416

African (AFR) AF: 0.733 AC: 30404 AN: 41478

American (AMR) AF: 0.795 AC: 12166 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.759 AC: 2634 AN: 3470

East Asian (EAS) AF: 0.939 AC: 4866 AN: 5182

South Asian (SAS) AF: 0.912 AC: 4408 AN: 4832

European-Finnish (FIN) AF: 0.829 AC: 8782 AN: 10590

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.766 AC: 52064 AN: 68008

Other (OTH) AF: 0.765 AC: 1617 AN: 2114

Alfa AF: 0.764 Hom.: 9098

Bravo AF: 0.764

Asia WGS AF: 0.908 AC: 3155 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	CHARGE syndrome (1)
-	-	1	Hypogonadotropic hypogonadism 5 with or without anosmia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.42
DANN	Benign	0.61
PhyloP100		-0.013
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: rs7836586; hg19: chr8-61655690;