1-6136457-G-A

Variant names:

• chr1-6136457-G-A
• rs7513548
• NM_015557.3:c.2696+60C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000262450.8(CHD5):​c.2696+60C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 1,594,072 control chromosomes in the GnomAD database, including 156,087 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.43 (14579 hom., cov: 32)
  • Exomes 𝑓: 0.43 (141508 hom.)
• Consequence: CHD5 ENST00000262450.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36
• Publications: 7 publications found

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]

CHD5 Gene-Disease associations (from GenCC):

• parenti-mignot neurodevelopmental syndrome

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• schizophrenia

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000262450.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD5	NM_015557.3	MANE Select	c.2696+60C>T		intron	N/A	NP_056372.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD5	ENST00000262450.8	TSL:1 MANE Select	c.2696+60C>T		intron	N/A	ENSP00000262450.3
	CHD5	ENST00000462991.5	TSL:1	n.842+60C>T		intron	N/A	ENSP00000466706.1
	CHD5	ENST00000496404.1	TSL:2	n.2696+60C>T		intron	N/A	ENSP00000433676.1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64689 AN: 151932 Hom.: 14567 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.429

GnomAD4 exome AF: 0.433 AC: 624251 AN: 1442022 Hom.: 141508 AF XY: 0.437 AC XY: 313009 AN XY: 715564

African (AFR) AF: 0.338 AC: 11127 AN: 32964

American (AMR) AF: 0.486 AC: 21116 AN: 43480

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 12713 AN: 25416

East Asian (EAS) AF: 0.829 AC: 32606 AN: 39352

South Asian (SAS) AF: 0.597 AC: 50709 AN: 84890

European-Finnish (FIN) AF: 0.535 AC: 28324 AN: 52920

Middle Eastern (MID) AF: 0.518 AC: 2194 AN: 4238

European-Non Finnish (NFE) AF: 0.399 AC: 438900 AN: 1099402

Other (OTH) AF: 0.447 AC: 26562 AN: 59360

GnomAD4 genome AF: 0.426 AC: 64748 AN: 152050 Hom.: 14579 Cov.: 32 AF XY: 0.435 AC XY: 32335 AN XY: 74314

African (AFR) AF: 0.340 AC: 14110 AN: 41490

American (AMR) AF: 0.450 AC: 6880 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1713 AN: 3464

East Asian (EAS) AF: 0.808 AC: 4163 AN: 5152

South Asian (SAS) AF: 0.604 AC: 2916 AN: 4826

European-Finnish (FIN) AF: 0.549 AC: 5795 AN: 10556

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27746 AN: 67968

Other (OTH) AF: 0.431 AC: 908 AN: 2106

Alfa AF: 0.418 Hom.: 1728

Bravo AF: 0.416

Asia WGS AF: 0.679 AC: 2357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.28
DANN	Benign	0.68
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7513548; hg19: chr1-6196517; COSMIC: COSV52422478; COSMIC: COSV52422478;