1-6109928-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_015557.3(CHD5):c.5445G>A(p.Thr1815=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00356 in 1,605,722 control chromosomes in the GnomAD database, including 155 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (80 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (75 hom.)
• Consequence: CHD5 NM_015557.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.834

Genes affected

CHD5 (HGNC:16816): (chromodomain helicase DNA binding protein 5) This gene encodes a member of the chromodomain helicase DNA-binding protein family. Members of this family are characterized by a chromodomain, a helicase ATP-binding domain and an additional functional domain. This gene encodes a neuron-specific protein that may function in chromatin remodeling and gene transcription. This gene is a potential tumor suppressor gene that may play a role in the development of neuroblastoma. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BP6: Variant 1-6109928-C-T is Benign according to our data. Variant chr1-6109928-C-T is described in ClinVar as [Benign]. Clinvar id is 782353.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.834 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHD5	NM_015557.3	c.5445G>A	p.Thr1815=	synonymous_variant	38/42	ENST00000262450.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHD5	ENST00000262450.8	c.5445G>A	p.Thr1815=	synonymous_variant	38/42	1	NM_015557.3	P1
CHD5	ENST00000462991.5	c.*517G>A		3_prime_UTR_variant, NMD_transcript_variant	28/31	1
CHD5	ENST00000377999.5	c.*2015G>A		3_prime_UTR_variant, NMD_transcript_variant	18/21	2
CHD5	ENST00000496404.1	c.*485G>A		3_prime_UTR_variant, NMD_transcript_variant	30/34	2

Frequencies

GnomAD3 genomes AF: 0.0190 AC: 2887 AN: 152108 Hom.: 80 Cov.: 33

Gnomad AFR AF: 0.0656

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00792

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.00512 AC: 1226 AN: 239572 Hom.: 38 AF XY: 0.00375 AC XY: 487 AN XY: 129914

Gnomad AFR exome AF: 0.0673

Gnomad AMR exome AF: 0.00341

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000137

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000158

Gnomad OTH exome AF: 0.00239

GnomAD4 exome AF: 0.00195 AC: 2828 AN: 1453496 Hom.: 75 Cov.: 32 AF XY: 0.00170 AC XY: 1227 AN XY: 722952

Gnomad4 AFR exome AF: 0.0655

Gnomad4 AMR exome AF: 0.00375

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000164

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000207

Gnomad4 OTH exome AF: 0.00390

GnomAD4 genome AF: 0.0190 AC: 2892 AN: 152226 Hom.: 80 Cov.: 33 AF XY: 0.0188 AC XY: 1399 AN XY: 74422

Gnomad4 AFR AF: 0.0655

Gnomad4 AMR AF: 0.00791

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00116 Hom.: 3

Bravo AF: 0.0202

Asia WGS AF: 0.00404 AC: 14 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

Invitae

Jul 31, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
Cadd	Benign	14
Dann	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs116111541; hg19: chr1-6169988;