rs71245513

Variant names:

• chr8-60678791-AGCGGCGGCGGCG-A
• rs71245513
• NM_017780.4:c.-456_-445delGCGGCGGCGGCG

Your query was ambiguous. Multiple possible variants found:

• chr8-60678791-AGCGGCGGCGGCG-A
• chr8-60678791-AGCGGCGGCGGCG-AGCGGCG
• chr8-60678791-AGCGGCGGCGGCG-AGCGGCGGCG
• chr8-60678791-AGCGGCGGCGGCG-AGCGGCGGCGGCGGCG
• chr8-60678791-AGCGGCGGCGGCG-AGCGGCGGCGGCGGCGGCG
• chr8-60678791-AGCGGCGGCGGCG-AGCGGCGGCGGCGGCGGCGGCG
• chr8-60678791-AGCGGCGGCGGCG-AGCGGCGGCGGCGGCGGCGGCGGCG
• chr8-60678791-AGCGGCGGCGGCG-AGCGGCGGCGGCGGCGGCGGCGGCGGCG
• chr8-60678791-AGCGGCGGCGGCG-AGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG
• chr8-60678791-AGCGGCGGCGGCG-AGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG
• chr8-60678791-AGCGGCGGCGGCG-AGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG
• chr8-60678791-AGCGGCGGCGGCG-AGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_017780.4(CHD7):​c.-456_-445delGCGGCGGCGGCG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 48,834 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 22)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHD7 NM_017780.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD7	NM_017780.4	c.-456_-445delGCGGCGGCGGCG		5_prime_UTR_variant	Exon 1 of 38	ENST00000423902.7	NP_060250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD7	ENST00000423902.7	c.-456_-445delGCGGCGGCGGCG		5_prime_UTR_variant	Exon 1 of 38	5	NM_017780.4	ENSP00000392028.1

Frequencies

GnomAD3 genomes AF: 0.0000205 AC: 1 AN: 48834 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000735

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1436 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 766

African (AFR) AF: 0.00 AC: 0 AN: 18

American (AMR) AF: 0.00 AC: 0 AN: 10

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 678

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 8

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 678

Other (OTH) AF: 0.00 AC: 0 AN: 32

GnomAD4 genome AF: 0.0000205 AC: 1 AN: 48834 Hom.: 0 Cov.: 22 AF XY: 0.0000424 AC XY: 1 AN XY: 23562

African (AFR) AF: 0.0000735 AC: 1 AN: 13602

American (AMR) AF: 0.00 AC: 0 AN: 5244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1344

East Asian (EAS) AF: 0.00 AC: 0 AN: 1184

South Asian (SAS) AF: 0.00 AC: 0 AN: 1232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 106

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 22600

Other (OTH) AF: 0.00 AC: 0 AN: 704

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs71245513; hg19: chr8-61591350;