rs7844902

Variant names:

• chr8-60838301-A-G
• rs7844902
• NM_017780.4:c.4533+46A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-60838301-A-G
• chr8-60838301-A-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.4533+46A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.768 in 1,534,680 control chromosomes in the GnomAD database, including 455,325 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (46707 hom., cov: 32)
  • Exomes 𝑓: 0.77 (408618 hom.)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.52
• Publications: 15 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=-0.92).
• BP6: Variant 8-60838301-A-G is Benign according to our data. Variant chr8-60838301-A-G is described in ClinVar as Benign. ClinVar VariationId is 158327.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.4533+46A>G		intron	N/A	NP_060250.2
	CHD7	NM_001316690.1		c.1717-23928A>G		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.4533+46A>G		intron	N/A	ENSP00000392028.1	Q9P2D1-1
	CHD7	ENST00000524602.5	TSL:1	c.1717-23928A>G		intron	N/A	ENSP00000437061.1	Q9P2D1-4
	CHD7	ENST00000933299.1		c.4533+46A>G		intron	N/A	ENSP00000603358.1

Frequencies

GnomAD3 genomes AF: 0.782 AC: 118854 AN: 152050 Hom.: 46676 Cov.: 32

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.898

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.729

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.755

GnomAD2 exomes AF: 0.804 AC: 148968 AN: 185184 AF XY: 0.807

Gnomad AFR exome AF: 0.789

Gnomad AMR exome AF: 0.812

Gnomad ASJ exome AF: 0.752

Gnomad EAS exome AF: 0.939

Gnomad FIN exome AF: 0.839

Gnomad NFE exome AF: 0.755

Gnomad OTH exome AF: 0.768

GnomAD4 exome AF: 0.767 AC: 1060240 AN: 1382512 Hom.: 408618 Cov.: 22 AF XY: 0.770 AC XY: 527835 AN XY: 685512

African (AFR) AF: 0.784 AC: 24939 AN: 31808

American (AMR) AF: 0.808 AC: 29973 AN: 37110

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 18954 AN: 25106

East Asian (EAS) AF: 0.938 AC: 35376 AN: 37716

South Asian (SAS) AF: 0.889 AC: 70404 AN: 79170

European-Finnish (FIN) AF: 0.833 AC: 42389 AN: 50858

Middle Eastern (MID) AF: 0.759 AC: 4274 AN: 5632

European-Non Finnish (NFE) AF: 0.746 AC: 788895 AN: 1057336

Other (OTH) AF: 0.779 AC: 45036 AN: 57776

GnomAD4 genome AF: 0.782 AC: 118938 AN: 152168 Hom.: 46707 Cov.: 32 AF XY: 0.790 AC XY: 58806 AN XY: 74398

African (AFR) AF: 0.780 AC: 32348 AN: 41488

American (AMR) AF: 0.792 AC: 12113 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.743 AC: 2577 AN: 3468

East Asian (EAS) AF: 0.939 AC: 4872 AN: 5188

South Asian (SAS) AF: 0.897 AC: 4329 AN: 4824

European-Finnish (FIN) AF: 0.829 AC: 8788 AN: 10598

Middle Eastern (MID) AF: 0.733 AC: 214 AN: 292

European-Non Finnish (NFE) AF: 0.757 AC: 51463 AN: 68000

Other (OTH) AF: 0.757 AC: 1594 AN: 2106

Alfa AF: 0.772 Hom.: 16992

Bravo AF: 0.773

Asia WGS AF: 0.914 AC: 3178 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	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	-0.92
CADD	Benign	0.023
DANN	Benign	0.31
PhyloP100		-1.5
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: rs7844902; hg19: chr8-61750860;