rs10092214

Variant names:

• chr8-60814320-G-A
• rs10092214
• NM_017780.4:c.2499-2067G>A

Variant summary

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

The NM_017780.4(CHD7):​c.2499-2067G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 152,140 control chromosomes in the GnomAD database, including 13,340 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 0.38 (13340 hom., cov: 33)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.653
• Publications: 6 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD7	NM_017780.4	c.2499-2067G>A		intron_variant	Intron 7 of 37	ENST00000423902.7	NP_060250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD7	ENST00000423902.7	c.2499-2067G>A		intron_variant	Intron 7 of 37	5	NM_017780.4	ENSP00000392028.1
CHD7	ENST00000524602.5	c.1716+33270G>A		intron_variant	Intron 2 of 4	1		ENSP00000437061.1
CHD7	ENST00000525508.1	c.2499-2067G>A		intron_variant	Intron 6 of 11	5		ENSP00000436027.1
CHD7	ENST00000695853.1	n.2499-2067G>A		intron_variant	Intron 7 of 36			ENSP00000512218.1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57406 AN: 152022 Hom.: 13339 Cov.: 33

Gnomad AFR AF: 0.0955

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.377 AC: 57419 AN: 152140 Hom.: 13340 Cov.: 33 AF XY: 0.386 AC XY: 28711 AN XY: 74344

African (AFR) AF: 0.0953 AC: 3960 AN: 41546

American (AMR) AF: 0.499 AC: 7635 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 1698 AN: 3468

East Asian (EAS) AF: 0.503 AC: 2606 AN: 5184

South Asian (SAS) AF: 0.504 AC: 2431 AN: 4820

European-Finnish (FIN) AF: 0.522 AC: 5510 AN: 10554

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.474 AC: 32226 AN: 67962

Other (OTH) AF: 0.403 AC: 851 AN: 2114

Alfa AF: 0.439 Hom.: 48613

Bravo AF: 0.363

Asia WGS AF: 0.429 AC: 1492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.32
DANN	Benign	0.34
PhyloP100		-0.65
Mutation Taster		=99/1	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: rs10092214; hg19: chr8-61726879;