rs6471895

Variant names:

• chr8-60712390-T-C
• rs6471895
• NM_017780.4:c.-174-28869T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017780.4(CHD7):​c.-174-28869T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0965 in 152,238 control chromosomes in the GnomAD database, including 1,515 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 0.096 (1515 hom., cov: 32)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.441
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD7	NM_017780.4	c.-174-28869T>C		intron_variant	Intron 1 of 37	ENST00000423902.7	NP_060250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD7	ENST00000423902.7	c.-174-28869T>C		intron_variant	Intron 1 of 37	5	NM_017780.4	ENSP00000392028.1

Frequencies

GnomAD3 genomes AF: 0.0964 AC: 14669 AN: 152120 Hom.: 1512 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0512

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.00769

Gnomad SAS AF: 0.0681

Gnomad FIN AF: 0.0243

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0329

Gnomad OTH AF: 0.0824

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0965 AC: 14690 AN: 152238 Hom.: 1515 Cov.: 32 AF XY: 0.0943 AC XY: 7019 AN XY: 74446

African (AFR) AF: 0.258 AC: 10718 AN: 41500

American (AMR) AF: 0.0510 AC: 781 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0392 AC: 136 AN: 3468

East Asian (EAS) AF: 0.00752 AC: 39 AN: 5188

South Asian (SAS) AF: 0.0671 AC: 324 AN: 4826

European-Finnish (FIN) AF: 0.0243 AC: 258 AN: 10614

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0329 AC: 2240 AN: 68024

Other (OTH) AF: 0.0829 AC: 175 AN: 2110

Alfa AF: 0.0752 Hom.: 169

Bravo AF: 0.104

Asia WGS AF: 0.0540 AC: 190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.34
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6471895; hg19: chr8-61624949;