chr8-60819981-AACTTTTTTTTTTCCCTTTGGTG-A

Variant names:

• chr8-60819981-AACTTTTTTTTTTCCCTTTGGTG-A
• rs886038633
• NM_017780.4:c.2614-25_2614-4delACTTTTTTTTTTCCCTTTGGTG

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_017780.4(CHD7):​c.2614-25_2614-4delACTTTTTTTTTTCCCTTTGGTG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHD7 NM_017780.4 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.49
• 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: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 8-60819981-AACTTTTTTTTTTCCCTTTGGTG-A is Benign according to our data. Variant chr8-60819981-AACTTTTTTTTTTCCCTTTGGTG-A is described in ClinVar as Likely_benign. ClinVar VariationId is 260896.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD7	NM_017780.4	c.2614-25_2614-4delACTTTTTTTTTTCCCTTTGGTG		splice_region_variant, intron_variant	Intron 8 of 37	ENST00000423902.7	NP_060250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD7	ENST00000423902.7	c.2614-25_2614-4delACTTTTTTTTTTCCCTTTGGTG		splice_region_variant, intron_variant	Intron 8 of 37	5	NM_017780.4	ENSP00000392028.1
CHD7	ENST00000524602.5	c.1716+38932_1716+38953delACTTTTTTTTTTCCCTTTGGTG		intron_variant	Intron 2 of 4	1		ENSP00000437061.1
CHD7	ENST00000525508.1	c.2614-25_2614-4delACTTTTTTTTTTCCCTTTGGTG		splice_region_variant, intron_variant	Intron 7 of 11	5		ENSP00000436027.1
CHD7	ENST00000695853.1	n.2614-25_2614-4delACTTTTTTTTTTCCCTTTGGTG		splice_region_variant, intron_variant	Intron 8 of 36			ENSP00000512218.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.5
BranchPoint Hunter		6.0

Splicing

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

Other links and lift over

dbSNP: rs886038633; hg19: chr8-61732540;