8-60740951-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_017780.4(CHD7):c.-174-308G>A variant causes a intron change. The variant allele was found at a frequency of 0.0113 in 152,304 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.011 (27 hom., cov: 32)
• Consequence: CHD7 NM_017780.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.94

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 8-60740951-G-A is Benign according to our data. Variant chr8-60740951-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1179969.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0113 (1723/152304) while in subpopulation NFE AF= 0.0196 (1330/68018). AF 95% confidence interval is 0.0187. There are 27 homozygotes in gnomad4. There are 750 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1723 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHD7	NM_017780.4	c.-174-308G>A		intron_variant		ENST00000423902.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHD7	ENST00000423902.7	c.-174-308G>A		intron_variant		5	NM_017780.4	P1

Frequencies

GnomAD3 genomes AF: 0.0113 AC: 1723 AN: 152186 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.00343

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00785

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00490

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0196

Gnomad OTH AF: 0.00907

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

GnomAD4 genome AF: 0.0113 AC: 1723 AN: 152304 Hom.: 27 Cov.: 32 AF XY: 0.0101 AC XY: 750 AN XY: 74466

Gnomad4 AFR AF: 0.00342

Gnomad4 AMR AF: 0.00784

Gnomad4 ASJ AF: 0.0124

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00490

Gnomad4 NFE AF: 0.0196

Gnomad4 OTH AF: 0.00898

Alfa AF: 0.0111 Hom.: 1

Bravo AF: 0.0120

Asia WGS AF: 0.00173 AC: 7 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
Cadd	Benign	20
Dann	Benign	0.88

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

Publications

LitVar

Other links and lift over

dbSNP: rs74350073; hg19: chr8-61653510;