dbSNP rs161740: CHD1:c.4107+428G>T (chr5-98869326-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001270.4(CHD1):c.4107+428G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 944,604 control chromosomes in the GnomAD database, including 36,839 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 0.27 ( 5908 hom., cov: 32)

Exomes 𝑓: 0.28 ( 30931 hom. )

Consequence

CHD1
NM_001270.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.442

Publications

4 publications found

Variant links:

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

CHD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD1	NM_001270.4 link	c.4107+428G>T		intron_variant	Intron 30 of 35	ENST00000614616.5	NP_001261.2	O14646-1B3KT33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD1	ENST00000614616.5 link	c.4107+428G>T		intron_variant	Intron 30 of 35	5	NM_001270.4	ENSP00000483667.1		O14646-1

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40705

AN:

151806

Hom.:

5904

Cov.:

show subpopulations

Gnomad AFR

AF:

0.356

Gnomad AMI

AF:

0.204

Gnomad AMR

AF:

0.209

Gnomad ASJ

AF:

0.353

Gnomad EAS

AF:

0.0521

Gnomad SAS

AF:

0.167

Gnomad FIN

AF:

0.147

Gnomad MID

AF:

0.338

Gnomad NFE

AF:

0.267

Gnomad OTH

AF:

0.271

GnomAD4 exome

AF:

0.277

AC:

219273

AN:

792680

Hom.:

30931

Cov.:

AF XY:

0.276

AC XY:

101487

AN XY:

367680

show subpopulations

African (AFR)

AF:

0.371

AC:

5553

AN:

14948

American (AMR)

AF:

0.184

AC:

197

AN:

1068

Ashkenazi Jewish (ASJ)

AF:

0.352

AC:

1733

AN:

4922

East Asian (EAS)

AF:

0.0466

AC:

162

AN:

3478

South Asian (SAS)

AF:

0.182

AC:

2862

AN:

15760

European-Finnish (FIN)

AF:

0.166

AC:

127

AN:

766

Middle Eastern (MID)

AF:

0.330

AC:

512

AN:

1552

European-Non Finnish (NFE)

AF:

0.277

AC:

200908

AN:

724202

Other (OTH)

AF:

0.278

AC:

7219

AN:

25984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

7055

14110

21164

28219

35274

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.268

AC:

40727

AN:

151924

Hom.:

5908

Cov.:

AF XY:

0.259

AC XY:

19219

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.356

AC:

14752

AN:

41438

American (AMR)

AF:

0.208

AC:

3180

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.353

AC:

1225

AN:

3470

East Asian (EAS)

AF:

0.0521

AC:

269

AN:

5168

South Asian (SAS)

AF:

0.165

AC:

798

AN:

4822

European-Finnish (FIN)

AF:

0.147

AC:

1550

AN:

10538

Middle Eastern (MID)

AF:

0.339

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.267

AC:

18104

AN:

67908

Other (OTH)

AF:

0.268

AC:

564

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1502

3005

4507

6010

7512

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.265

Hom.:

8474

Bravo

AF:

0.279

Asia WGS

AF:

0.131

AC:

454

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.71

(source)

DANN

Benign

0.58

PhyloP100

-0.44

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs161740

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over