rs6471902

Variant names:

• chr8-60819962-A-G
• rs6471902
• NM_017780.4:c.2614-45A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-60819962-A-G
• chr8-60819962-A-C
• chr8-60819962-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.2614-45A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 1,283,818 control chromosomes in the GnomAD database, including 401,297 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.80 (48685 hom., cov: 32)
  • Exomes 𝑓: 0.79 (352612 hom.)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.989
• 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=-0.84).
• BP6: Variant 8-60819962-A-G is Benign according to our data. Variant chr8-60819962-A-G is described in ClinVar as Benign. ClinVar VariationId is 158326.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.2614-45A>G		intron	N/A	NP_060250.2
	CHD7	NM_001316690.1		c.1716+38912A>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.2614-45A>G		intron	N/A	ENSP00000392028.1	Q9P2D1-1
	CHD7	ENST00000524602.5	TSL:1	c.1716+38912A>G		intron	N/A	ENSP00000437061.1	Q9P2D1-4
	CHD7	ENST00000933299.1		c.2614-45A>G		intron	N/A	ENSP00000603358.1

Frequencies

GnomAD3 genomes AF: 0.799 AC: 121459 AN: 152036 Hom.: 48661 Cov.: 32

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.903

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.774

GnomAD2 exomes AF: 0.817 AC: 135194 AN: 165404 AF XY: 0.820

Gnomad AFR exome AF: 0.812

Gnomad AMR exome AF: 0.827

Gnomad ASJ exome AF: 0.765

Gnomad EAS exome AF: 0.939

Gnomad FIN exome AF: 0.839

Gnomad NFE exome AF: 0.772

Gnomad OTH exome AF: 0.785

GnomAD4 exome AF: 0.788 AC: 891354 AN: 1131664 Hom.: 352612 Cov.: 15 AF XY: 0.791 AC XY: 451966 AN XY: 571566

African (AFR) AF: 0.802 AC: 21304 AN: 26566

American (AMR) AF: 0.824 AC: 29246 AN: 35500

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 18098 AN: 23492

East Asian (EAS) AF: 0.938 AC: 33081 AN: 35270

South Asian (SAS) AF: 0.895 AC: 65909 AN: 73620

European-Finnish (FIN) AF: 0.837 AC: 40148 AN: 47986

Middle Eastern (MID) AF: 0.771 AC: 3965 AN: 5144

European-Non Finnish (NFE) AF: 0.767 AC: 640268 AN: 834690

Other (OTH) AF: 0.796 AC: 39335 AN: 49396

GnomAD4 genome AF: 0.799 AC: 121537 AN: 152154 Hom.: 48685 Cov.: 32 AF XY: 0.807 AC XY: 60014 AN XY: 74384

African (AFR) AF: 0.800 AC: 33195 AN: 41494

American (AMR) AF: 0.813 AC: 12434 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 2643 AN: 3468

East Asian (EAS) AF: 0.939 AC: 4868 AN: 5184

South Asian (SAS) AF: 0.903 AC: 4361 AN: 4830

European-Finnish (FIN) AF: 0.832 AC: 8807 AN: 10586

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.775 AC: 52705 AN: 67984

Other (OTH) AF: 0.776 AC: 1638 AN: 2110

Alfa AF: 0.762 Hom.: 6557

Bravo AF: 0.791

Asia WGS AF: 0.913 AC: 3173 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	-0.84
CADD	Benign	1.7
DANN	Benign	0.70
PhyloP100		0.99
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: rs6471902; hg19: chr8-61732521;