rs41272442

Variant names:

• chr8-60830287-C-G
• rs41272442
• NM_017780.4:c.3523-35C>G

Your query was ambiguous. Multiple possible variants found:

• chr8-60830287-C-G
• chr8-60830287-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017780.4(CHD7):​c.3523-35C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0175 in 1,577,700 control chromosomes in the GnomAD database, including 1,345 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.058 (702 hom., cov: 32)
  • Exomes 𝑓: 0.013 (643 hom.)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.524
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 8-60830287-C-G is Benign according to our data. Variant chr8-60830287-C-G is described in ClinVar as Benign. ClinVar VariationId is 260903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD7	NM_017780.4	c.3523-35C>G		intron_variant	Intron 14 of 37	ENST00000423902.7	NP_060250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD7	ENST00000423902.7	c.3523-35C>G		intron_variant	Intron 14 of 37	5	NM_017780.4	ENSP00000392028.1
CHD7	ENST00000524602.5	c.1717-31942C>G		intron_variant	Intron 2 of 4	1		ENSP00000437061.1
CHD7	ENST00000695853.1	n.3523-35C>G		intron_variant	Intron 14 of 36			ENSP00000512218.1

Frequencies

GnomAD3 genomes AF: 0.0578 AC: 8787 AN: 152086 Hom.: 694 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0318

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00636

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.00123

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00816

Gnomad OTH AF: 0.0435

GnomAD2 exomes AF: 0.0199 AC: 4476 AN: 224874 AF XY: 0.0173

Gnomad AFR exome AF: 0.183

Gnomad AMR exome AF: 0.0128

Gnomad ASJ exome AF: 0.000478

Gnomad EAS exome AF: 0.00694

Gnomad FIN exome AF: 0.00121

Gnomad NFE exome AF: 0.00805

Gnomad OTH exome AF: 0.0126

GnomAD4 exome AF: 0.0131 AC: 18714 AN: 1425496 Hom.: 643 Cov.: 30 AF XY: 0.0127 AC XY: 8952 AN XY: 707212

African (AFR) AF: 0.182 AC: 5708 AN: 31310

American (AMR) AF: 0.0142 AC: 537 AN: 37864

Ashkenazi Jewish (ASJ) AF: 0.000691 AC: 17 AN: 24614

East Asian (EAS) AF: 0.00683 AC: 269 AN: 39382

South Asian (SAS) AF: 0.0141 AC: 1136 AN: 80588

European-Finnish (FIN) AF: 0.00139 AC: 73 AN: 52548

Middle Eastern (MID) AF: 0.0176 AC: 96 AN: 5466

European-Non Finnish (NFE) AF: 0.00876 AC: 9588 AN: 1095034

Other (OTH) AF: 0.0220 AC: 1290 AN: 58690

GnomAD4 genome AF: 0.0579 AC: 8820 AN: 152204 Hom.: 702 Cov.: 32 AF XY: 0.0567 AC XY: 4223 AN XY: 74432

African (AFR) AF: 0.182 AC: 7563 AN: 41498

American (AMR) AF: 0.0317 AC: 485 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00618 AC: 32 AN: 5178

South Asian (SAS) AF: 0.0143 AC: 69 AN: 4830

European-Finnish (FIN) AF: 0.00123 AC: 13 AN: 10594

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00816 AC: 555 AN: 68022

Other (OTH) AF: 0.0459 AC: 97 AN: 2114

Alfa AF: 0.0288 Hom.: 53

Bravo AF: 0.0651

Asia WGS AF: 0.0360 AC: 123 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.1
DANN	Benign	0.73
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs41272442; hg19: chr8-61742846;