rs2068096

Variant names:

• chr8-60853001-G-A
• rs2068096
• NM_017780.4:c.6276G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-60853001-G-A
• chr8-60853001-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_017780.4(CHD7):​c.6276G>A​(p.Glu2092Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0534 in 1,613,912 control chromosomes in the GnomAD database, including 5,201 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (2167 hom., cov: 32)
  • Exomes 𝑓: 0.047 (3034 hom.)
• Consequence: CHD7 NM_017780.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:14
• Conservation: PhyloP100: 1.44
• Publications: 9 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 8-60853001-G-A is Benign according to our data. Variant chr8-60853001-G-A is described in ClinVar as Benign. ClinVar VariationId is 95802.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.44 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.301 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.6276G>A	p.Glu2092Glu	synonymous	Exon 31 of 38	NP_060250.2
	CHD7	NM_001316690.1		c.1717-9228G>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.6276G>A	p.Glu2092Glu	synonymous	Exon 31 of 38	ENSP00000392028.1	Q9P2D1-1
	CHD7	ENST00000524602.5	TSL:1	c.1717-9228G>A		intron	N/A	ENSP00000437061.1	Q9P2D1-4
	CHD7	ENST00000933299.1		c.6312G>A	p.Glu2104Glu	synonymous	Exon 31 of 38	ENSP00000603358.1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17995 AN: 152084 Hom.: 2170 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0637

Gnomad ASJ AF: 0.0688

Gnomad EAS AF: 0.0160

Gnomad SAS AF: 0.0478

Gnomad FIN AF: 0.0756

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0406

Gnomad OTH AF: 0.103

GnomAD2 exomes AF: 0.0611 AC: 15230 AN: 249160 AF XY: 0.0572

Gnomad AFR exome AF: 0.317

Gnomad AMR exome AF: 0.0359

Gnomad ASJ exome AF: 0.0749

Gnomad EAS exome AF: 0.0132

Gnomad FIN exome AF: 0.0804

Gnomad NFE exome AF: 0.0407

Gnomad OTH exome AF: 0.0565

GnomAD4 exome AF: 0.0466 AC: 68184 AN: 1461710 Hom.: 3034 Cov.: 33 AF XY: 0.0458 AC XY: 33281 AN XY: 727138

African (AFR) AF: 0.315 AC: 10553 AN: 33478

American (AMR) AF: 0.0399 AC: 1784 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0754 AC: 1971 AN: 26136

East Asian (EAS) AF: 0.0165 AC: 657 AN: 39700

South Asian (SAS) AF: 0.0474 AC: 4086 AN: 86258

European-Finnish (FIN) AF: 0.0784 AC: 4187 AN: 53402

Middle Eastern (MID) AF: 0.0706 AC: 407 AN: 5768

European-Non Finnish (NFE) AF: 0.0368 AC: 40965 AN: 1111870

Other (OTH) AF: 0.0592 AC: 3574 AN: 60374

GnomAD4 genome AF: 0.118 AC: 18002 AN: 152202 Hom.: 2167 Cov.: 32 AF XY: 0.117 AC XY: 8712 AN XY: 74412

African (AFR) AF: 0.305 AC: 12670 AN: 41500

American (AMR) AF: 0.0636 AC: 973 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0688 AC: 239 AN: 3472

East Asian (EAS) AF: 0.0159 AC: 82 AN: 5170

South Asian (SAS) AF: 0.0472 AC: 228 AN: 4826

European-Finnish (FIN) AF: 0.0756 AC: 802 AN: 10608

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0406 AC: 2760 AN: 68008

Other (OTH) AF: 0.102 AC: 216 AN: 2114

Alfa AF: 0.0671 Hom.: 1281

Bravo AF: 0.123

Asia WGS AF: 0.0440 AC: 154 AN: 3478

EpiCase AF: 0.0376

EpiControl AF: 0.0381

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	8	not specified (8)
-	-	3	not provided (3)
-	-	1	CHARGE syndrome (1)
-	-	1	Hypogonadotropic hypogonadism 5 with or without anosmia (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	2.1
DANN	Benign	0.44
PhyloP100		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
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: rs2068096; hg19: chr8-61765560;