5-98869326-C-T

Variant names:

• chr5-98869326-C-T
• rs161740
• NM_001270.4:c.4107+428G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001364113.3(CHD1):​c.4108-49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00292 in 945,954 control chromosomes in the GnomAD database, including 10 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 0.0014 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (9 hom.)
• Consequence: CHD1 NM_001364113.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442
• Publications: 4 publications found

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]

CHD1 Gene-Disease associations (from GenCC):

• Pilarowski-Bjornsson syndrome

  Inheritance: AD, Unknown Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet
• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00145 (220/151992) while in subpopulation NFE AF = 0.00255 (173/67940). AF 95% confidence interval is 0.00224. There are 1 homozygotes in GnomAd4. There are 97 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 9 AD,Unknown,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364113.3. 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
	CHD1	NM_001270.4	MANE Select	c.4107+428G>A		intron	N/A	NP_001261.2
	CHD1	NM_001364113.3		c.4108-49G>A		intron	N/A	NP_001351042.1
	CHD1	NM_001376194.2		c.4107+428G>A		intron	N/A	NP_001363123.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD1	ENST00000614616.5	TSL:5 MANE Select	c.4107+428G>A		intron	N/A	ENSP00000483667.1
	CHD1	ENST00000511067.3	TSL:5	c.4108-49G>A		intron	N/A	ENSP00000479403.2
	CHD1	ENST00000926040.1		c.4107+428G>A		intron	N/A	ENSP00000596099.1

Frequencies

GnomAD3 genomes AF: 0.00145 AC: 220 AN: 151874 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000726

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000787

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000949

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00255

Gnomad OTH AF: 0.00192

GnomAD4 exome AF: 0.00320 AC: 2538 AN: 793962 Hom.: 9 Cov.: 12 AF XY: 0.00314 AC XY: 1157 AN XY: 368274

African (AFR) AF: 0.000467 AC: 7 AN: 14986

American (AMR) AF: 0.00187 AC: 2 AN: 1072

Ashkenazi Jewish (ASJ) AF: 0.000203 AC: 1 AN: 4930

East Asian (EAS) AF: 0.00 AC: 0 AN: 3478

South Asian (SAS) AF: 0.0000634 AC: 1 AN: 15782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 766

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1556

European-Non Finnish (NFE) AF: 0.00336 AC: 2440 AN: 725364

Other (OTH) AF: 0.00334 AC: 87 AN: 26028

GnomAD4 genome AF: 0.00145 AC: 220 AN: 151992 Hom.: 1 Cov.: 32 AF XY: 0.00131 AC XY: 97 AN XY: 74318

African (AFR) AF: 0.000724 AC: 30 AN: 41460

American (AMR) AF: 0.000786 AC: 12 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.0000949 AC: 1 AN: 10542

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00255 AC: 173 AN: 67940

Other (OTH) AF: 0.00190 AC: 4 AN: 2108

Alfa AF: 0.00 Hom.: 8474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.4
DANN	Benign	0.60
PhyloP100		-0.44

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: rs161740; hg19: chr5-98205030;