5-98856460-AAGG-A

Position:

• chr5-98856460-AAGG-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PM4_Supporting BP6_Moderate BA1

The NM_001270.4(CHD1):​c.5050_5052del​(p.Pro1684del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,612,658 control chromosomes in the GnomAD database, including 56,094 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (5531 hom., cov: 21)
  • Exomes 𝑓: 0.26 (50563 hom.)
• Consequence: CHD1 NM_001270.4 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 8.81

Genes affected

CHD1 (HGNC:1915): (chromodomain helicase DNA binding protein 1) The CHD family of proteins is characterized by the presence of chromo (chromatin organization modifier) domains and SNF2-related helicase/ATPase domains. CHD genes alter gene expression possibly by modification of chromatin structure thus altering access of the transcriptional apparatus to its chromosomal DNA template. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001270.4. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 5-98856460-AAGG-A is Benign according to our data. Variant chr5-98856460-AAGG-A is described in ClinVar as [Benign]. Clinvar id is 1249419.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD1	NM_001270.4	c.5050_5052del	p.Pro1684del	inframe_deletion	36/36	ENST00000614616.5	NP_001261.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHD1	ENST00000614616.5	c.5050_5052del	p.Pro1684del	inframe_deletion	36/36	5	NM_001270.4	ENSP00000483667	P2

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39698 AN: 151776 Hom.: 5528 Cov.: 21

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.0516

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.266

GnomAD3 exomes AF: 0.217 AC: 54425 AN: 251198 Hom.: 6829 AF XY: 0.217 AC XY: 29452 AN XY: 135750

Gnomad AFR exome AF: 0.338

Gnomad AMR exome AF: 0.143

Gnomad ASJ exome AF: 0.341

Gnomad EAS exome AF: 0.0426

Gnomad SAS exome AF: 0.175

Gnomad FIN exome AF: 0.148

Gnomad NFE exome AF: 0.262

Gnomad OTH exome AF: 0.239

GnomAD4 exome AF: 0.256 AC: 374663 AN: 1460764 Hom.: 50563 AF XY: 0.254 AC XY: 184491 AN XY: 726696

Gnomad4 AFR exome AF: 0.341

Gnomad4 AMR exome AF: 0.151

Gnomad4 ASJ exome AF: 0.344

Gnomad4 EAS exome AF: 0.0667

Gnomad4 SAS exome AF: 0.176

Gnomad4 FIN exome AF: 0.153

Gnomad4 NFE exome AF: 0.273

Gnomad4 OTH exome AF: 0.264

GnomAD4 genome AF: 0.261 AC: 39718 AN: 151894 Hom.: 5531 Cov.: 21 AF XY: 0.252 AC XY: 18740 AN XY: 74286

Gnomad4 AFR AF: 0.335

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.0515

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.262

Alfa AF: 0.267 Hom.: 1038

Bravo AF: 0.272

Asia WGS AF: 0.129 AC: 449 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 01, 2020

- -

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: rs138635992; hg19: chr5-98192164;