rs12544305

Variant names:

• chr8-60685250-A-G
• rs12544305
• NM_017780.4:c.-175+6168A>G

Variant summary

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

The NM_017780.4(CHD7):​c.-175+6168A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 152,300 control chromosomes in the GnomAD database, including 51,679 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 0.82 (51679 hom., cov: 33)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.342
• Publications: 8 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD7	NM_017780.4	c.-175+6168A>G		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.-175+6168A>G		intron_variant	Intron 1 of 37	5	NM_017780.4	ENSP00000392028.1

Frequencies

GnomAD3 genomes AF: 0.821 AC: 124979 AN: 152182 Hom.: 51644 Cov.: 33

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.815

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.942

Gnomad SAS AF: 0.921

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.803

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

GnomAD4 genome AF: 0.821 AC: 125069 AN: 152300 Hom.: 51679 Cov.: 33 AF XY: 0.827 AC XY: 61594 AN XY: 74454

African (AFR) AF: 0.887 AC: 36872 AN: 41570

American (AMR) AF: 0.815 AC: 12472 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 2647 AN: 3472

East Asian (EAS) AF: 0.942 AC: 4895 AN: 5194

South Asian (SAS) AF: 0.921 AC: 4452 AN: 4832

European-Finnish (FIN) AF: 0.831 AC: 8804 AN: 10592

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.770 AC: 52348 AN: 68018

Other (OTH) AF: 0.805 AC: 1700 AN: 2112

Alfa AF: 0.803 Hom.: 8613

Bravo AF: 0.817

Asia WGS AF: 0.921 AC: 3200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.35
PhyloP100		-0.34
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: rs12544305; hg19: chr8-61597809;