rs13256023

Variant names:

• chr8-60735992-C-T
• rs13256023
• NM_017780.4:c.-174-5267C>T

Variant summary

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

The NM_017780.4(CHD7):​c.-174-5267C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,076 control chromosomes in the GnomAD database, including 7,576 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 0.28 (7576 hom., cov: 32)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• Publications: 12 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, Labcorp Genetics (formerly Invitae), 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.505 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.-174-5267C>T		intron	N/A	NP_060250.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD7	ENST00000423902.7	TSL:5 MANE Select	c.-174-5267C>T		intron	N/A	ENSP00000392028.1	Q9P2D1-1
	CHD7	ENST00000933299.1		c.-174-5267C>T		intron	N/A	ENSP00000603358.1
	CHD7	ENST00000933300.1		c.-174-5267C>T		intron	N/A	ENSP00000603359.1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42152 AN: 151958 Hom.: 7567 Cov.: 32

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.277 AC: 42191 AN: 152076 Hom.: 7576 Cov.: 32 AF XY: 0.273 AC XY: 20290 AN XY: 74326

African (AFR) AF: 0.511 AC: 21189 AN: 41446

American (AMR) AF: 0.222 AC: 3396 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 746 AN: 3468

East Asian (EAS) AF: 0.150 AC: 777 AN: 5182

South Asian (SAS) AF: 0.142 AC: 682 AN: 4818

European-Finnish (FIN) AF: 0.188 AC: 1985 AN: 10578

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12560 AN: 67986

Other (OTH) AF: 0.252 AC: 532 AN: 2112

Alfa AF: 0.217 Hom.: 13209

Bravo AF: 0.290

Asia WGS AF: 0.192 AC: 672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.43
DANN	Benign	0.67
PhyloP100		-1.6
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs13256023;

hg19: chr8-61648551;