rs752271550

Positions:

• chr8-60801516-CT-C
• chr8-60801516-CT-CTT

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The NM_017780.4(CHD7):​c.2377-3del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00029 in 1,512,270 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (0 hom.)
• Consequence: CHD7 NM_017780.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30

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 Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 8-60801516-CT-C is Benign according to our data. Variant chr8-60801516-CT-C is described in Lovd as [Benign].
• BS2: High AC in GnomAdExome4 at 438 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHD7	NM_017780.4	c.2377-3del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000423902.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHD7	ENST00000423902.7	c.2377-3del		splice_polypyrimidine_tract_variant, intron_variant		5	NM_017780.4	P1

Frequencies

GnomAD3 genomes AF: 0.00000664 AC: 1 AN: 150542 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000244

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 AF: 0.000322 AC: 438 AN: 1361728 Hom.: 0 Cov.: 29 AF XY: 0.000309 AC XY: 208 AN XY: 673316

Gnomad4 AFR exome AF: 0.000386

Gnomad4 AMR exome AF: 0.000616

Gnomad4 ASJ exome AF: 0.000327

Gnomad4 EAS exome AF: 0.000194

Gnomad4 SAS exome AF: 0.000300

Gnomad4 FIN exome AF: 0.000102

Gnomad4 NFE exome AF: 0.000320

Gnomad4 OTH exome AF: 0.000459

GnomAD4 genome AF: 0.00000664 AC: 1 AN: 150542 Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1 AN XY: 73404

Gnomad4 AFR AF: 0.0000244

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00361 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs752271550; hg19: chr8-61714075;