rs146540815

Variant names:

• chr5-98856583-G-A
• rs146540815
• NM_001270.4:c.4930C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-98856583-G-A
• chr5-98856583-G-C
• chr5-98856583-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_001270.4(CHD1):​c.4930C>T​(p.Arg1644Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,613,502 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1644G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: CHD1 NM_001270.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.36
• Publications: 1 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: Unknown, AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P
• complex neurodevelopmental disorder

  Inheritance: AR, AD Classification: LIMITED Submitted by: Ambry Genetics, ClinGen

ENSG00000295348 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0000592 (9/152008) while in subpopulation SAS AF = 0.000207 (1/4826). AF 95% confidence interval is 0.0000529. There are 0 homozygotes in GnomAd4. There are 4 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD1	NM_001270.4	MANE Select	c.4930C>T	p.Arg1644Trp	missense	Exon 36 of 36	NP_001261.2	O14646-1
	CHD1	NM_001364113.3		c.5194C>T	p.Arg1732Trp	missense	Exon 37 of 37	NP_001351042.1	A0A087WVF4
	CHD1	NM_001376194.2		c.4930C>T	p.Arg1644Trp	missense	Exon 36 of 36	NP_001363123.1	O14646-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD1	ENST00000614616.5	TSL:5 MANE Select	c.4930C>T	p.Arg1644Trp	missense	Exon 36 of 36	ENSP00000483667.1	O14646-1
	CHD1	ENST00000511067.3	TSL:5	c.5194C>T	p.Arg1732Trp	missense	Exon 37 of 37	ENSP00000479403.2	A0A087WVF4
	CHD1	ENST00000926040.1		c.4930C>T	p.Arg1644Trp	missense	Exon 36 of 36	ENSP00000596099.1

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152008 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000319 AC: 8 AN: 251124 AF XY: 0.0000442

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000869

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000363 AC: 53 AN: 1461494 Hom.: 0 Cov.: 33 AF XY: 0.0000330 AC XY: 24 AN XY: 727046

African (AFR) AF: 0.0000299 AC: 1 AN: 33472

American (AMR) AF: 0.0000895 AC: 4 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000387 AC: 43 AN: 1111708

Other (OTH) AF: 0.0000497 AC: 3 AN: 60372

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152008 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74254

African (AFR) AF: 0.00 AC: 0 AN: 41392

American (AMR) AF: 0.000197 AC: 3 AN: 15262

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67972

Other (OTH) AF: 0.000479 AC: 1 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000529

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.090	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.081	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Uncertain	0.71	D
MutationAssessor	Benign	0.69	N
PhyloP100		3.4
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.58
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.084	T
Polyphen		1.0	D
Vest4		0.51
MVP		0.81
MPC		0.099
ClinPred		0.30	T
GERP RS		4.5
Varity_R		0.084
gMVP		0.54
Mutation Taster		=72/28	polymorphism

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: rs146540815; hg19: chr5-98192287; COSMIC: COSV99399185;