8-60852279-C-T

Variant names:

• chr8-60852279-C-T
• rs41265252
• NM_017780.4:c.5894+32C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_017780.4(CHD7):​c.5894+32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,573,062 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0077 (17 hom., cov: 32)
  • Exomes 𝑓: 0.00099 (16 hom.)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00774 (1178/152240) while in subpopulation AFR AF = 0.026 (1079/41526). AF 95% confidence interval is 0.0247. There are 17 homozygotes in GnomAd4. There are 565 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 17 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD7	NM_017780.4	c.5894+32C>T		intron_variant	Intron 29 of 37	ENST00000423902.7	NP_060250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD7	ENST00000423902.7	c.5894+32C>T		intron_variant	Intron 29 of 37	5	NM_017780.4	ENSP00000392028.1
CHD7	ENST00000524602.5	c.1717-9950C>T		intron_variant	Intron 2 of 4	1		ENSP00000437061.1
CHD7	ENST00000527921.1	n.385+32C>T		intron_variant	Intron 4 of 4	4
CHD7	ENST00000695853.1	n.5894+32C>T		intron_variant	Intron 29 of 36			ENSP00000512218.1

Frequencies

GnomAD3 genomes AF: 0.00772 AC: 1174 AN: 152122 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.0260

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00327

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000660

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00765

GnomAD2 exomes AF: 0.00211 AC: 495 AN: 234198 AF XY: 0.00171

Gnomad AFR exome AF: 0.0255

Gnomad AMR exome AF: 0.00168

Gnomad ASJ exome AF: 0.00148

Gnomad EAS exome AF: 0.000113

Gnomad FIN exome AF: 0.000921

Gnomad NFE exome AF: 0.000304

Gnomad OTH exome AF: 0.000528

GnomAD4 exome AF: 0.000992 AC: 1409 AN: 1420822 Hom.: 16 Cov.: 25 AF XY: 0.000899 AC XY: 636 AN XY: 707444

African (AFR) AF: 0.0272 AC: 887 AN: 32580

American (AMR) AF: 0.00201 AC: 88 AN: 43700

Ashkenazi Jewish (ASJ) AF: 0.00107 AC: 27 AN: 25122

East Asian (EAS) AF: 0.000127 AC: 5 AN: 39438

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83640

European-Finnish (FIN) AF: 0.000846 AC: 44 AN: 51996

Middle Eastern (MID) AF: 0.000620 AC: 3 AN: 4842

European-Non Finnish (NFE) AF: 0.000222 AC: 240 AN: 1080696

Other (OTH) AF: 0.00194 AC: 114 AN: 58808

GnomAD4 genome AF: 0.00774 AC: 1178 AN: 152240 Hom.: 17 Cov.: 32 AF XY: 0.00759 AC XY: 565 AN XY: 74430

African (AFR) AF: 0.0260 AC: 1079 AN: 41526

American (AMR) AF: 0.00327 AC: 50 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000660 AC: 7 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68018

Other (OTH) AF: 0.00757 AC: 16 AN: 2114

Alfa AF: 0.000431 Hom.: 2

Bravo AF: 0.00853

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.62
DANN	Benign	0.75
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs41265252; hg19: chr8-61764838; COSMIC: COSV71112620; COSMIC: COSV71112620;