8-60819983-CT-C

Variant names:

• chr8-60819983-CT-C
• rs748282026
• NM_017780.4:c.2614-14delT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_017780.4(CHD7):​c.2614-14delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0223 in 1,268,764 control chromosomes in the GnomAD database, including 737 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (60 hom., cov: 33)
  • Exomes 𝑓: 0.023 (677 hom.)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.127
• Publications: 0 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: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, Broad Center for Mendelian Genomics, ClinGen, G2P
• 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 -16 ACMG points.

• BP6: Variant 8-60819983-CT-C is Benign according to our data. Variant chr8-60819983-CT-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 210715.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.111 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD7	NM_017780.4	MANE Select	c.2614-14delT		intron	N/A	NP_060250.2
	CHD7	NM_001316690.1		c.1716+38943delT		intron	N/A	NP_001303619.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD7	ENST00000423902.7	TSL:5 MANE Select	c.2614-23delT		intron	N/A	ENSP00000392028.1
	CHD7	ENST00000524602.5	TSL:1	c.1716+38934delT		intron	N/A	ENSP00000437061.1
	CHD7	ENST00000933299.1		c.2614-23delT		intron	N/A	ENSP00000603358.1

Frequencies

GnomAD3 genomes AF: 0.0152 AC: 2283 AN: 150312 Hom.: 60 Cov.: 33

Gnomad AFR AF: 0.00335

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0194

Gnomad ASJ AF: 0.0293

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.0661

Gnomad FIN AF: 0.00542

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0102

Gnomad OTH AF: 0.0267

GnomAD2 exomes AF: 0.0498 AC: 6281 AN: 126246 AF XY: 0.0527

Gnomad AFR exome AF: 0.0170

Gnomad AMR exome AF: 0.0367

Gnomad ASJ exome AF: 0.0589

Gnomad EAS exome AF: 0.163

Gnomad FIN exome AF: 0.0158

Gnomad NFE exome AF: 0.0289

Gnomad OTH exome AF: 0.0462

GnomAD4 exome AF: 0.0233 AC: 26014 AN: 1118342 Hom.: 677 Cov.: 20 AF XY: 0.0252 AC XY: 14028 AN XY: 557744

African (AFR) AF: 0.00836 AC: 214 AN: 25600

American (AMR) AF: 0.0259 AC: 803 AN: 30974

Ashkenazi Jewish (ASJ) AF: 0.0456 AC: 965 AN: 21140

East Asian (EAS) AF: 0.144 AC: 4829 AN: 33620

South Asian (SAS) AF: 0.0809 AC: 5190 AN: 64150

European-Finnish (FIN) AF: 0.00956 AC: 404 AN: 42272

Middle Eastern (MID) AF: 0.0935 AC: 457 AN: 4886

European-Non Finnish (NFE) AF: 0.0139 AC: 11775 AN: 848472

Other (OTH) AF: 0.0292 AC: 1377 AN: 47228

GnomAD4 genome AF: 0.0151 AC: 2275 AN: 150422 Hom.: 60 Cov.: 33 AF XY: 0.0166 AC XY: 1218 AN XY: 73402

African (AFR) AF: 0.00332 AC: 136 AN: 41010

American (AMR) AF: 0.0194 AC: 292 AN: 15064

Ashkenazi Jewish (ASJ) AF: 0.0293 AC: 101 AN: 3448

East Asian (EAS) AF: 0.119 AC: 611 AN: 5142

South Asian (SAS) AF: 0.0662 AC: 315 AN: 4760

European-Finnish (FIN) AF: 0.00542 AC: 56 AN: 10340

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0102 AC: 687 AN: 67376

Other (OTH) AF: 0.0279 AC: 58 AN: 2080

Alfa AF: 0.0227 Hom.: 6

Bravo AF: 0.0145

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.13
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: rs748282026; hg19: chr8-61732542; COSMIC: COSV71114594;