rs138975765

Variant names:

• chr5-98856659-A-C
• NM_001270.4:c.4854T>G

Your query was ambiguous. Multiple possible variants found:

• chr5-98856659-A-C
• chr5-98856659-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001270.4(CHD1):​c.4854T>G​(p.Asn1618Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CHD1 NM_001270.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10868439).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD1	NM_001270.4	c.4854T>G	p.Asn1618Lys	missense_variant	Exon 36 of 36	ENST00000614616.5	NP_001261.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD1	ENST00000614616.5	c.4854T>G	p.Asn1618Lys	missense_variant	Exon 36 of 36	5	NM_001270.4	ENSP00000483667.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461532 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727054

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.048	T;T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.29
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.84	.;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	0.69	N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.40	.;N
REVEL	Benign	0.15
Sift	Uncertain	0.029	.;D
Sift4G	Benign	0.93	T;T
Polyphen		0.0080	B;B
Vest4		0.25
MutPred		0.23		Gain of ubiquitination at N1618 (P = 0.0031);Gain of ubiquitination at N1618 (P = 0.0031);
MVP		0.66
MPC		0.040
ClinPred		0.062	T
GERP RS		0.70
Varity_R		0.058
gMVP		0.18

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-98192363;