2-219539625-C-G

Variant names:

• chr2-219539625-C-G
• rs142415191
• NM_024536.6:c.2086G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024536.6(CHPF):​c.2086G>C​(p.Glu696Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000552 in 1,613,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000050 (0 hom.)
• Consequence: CHPF NM_024536.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.31
• Publications: 6 publications found

Genes affected

CHPF (HGNC:24291): (chondroitin polymerizing factor) Enables N-acetylgalactosaminyl-proteoglycan 3-beta-glucuronosyltransferase activity and glucuronosyl-N-acetylgalactosaminyl-proteoglycan 4-beta-N-acetylgalactosaminyltransferase activity. Involved in chondroitin sulfate biosynthetic process. Predicted to be located in Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.020875812).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024536.6. 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
	CHPF	NM_024536.6	MANE Select	c.2086G>C	p.Glu696Gln	missense	Exon 4 of 4	NP_078812.3
	CHPF	NM_001195731.2		c.1600G>C	p.Glu534Gln	missense	Exon 4 of 4	NP_001182660.2	Q8IZ52-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHPF	ENST00000243776.11	TSL:1 MANE Select	c.2086G>C	p.Glu696Gln	missense	Exon 4 of 4	ENSP00000243776.6	Q8IZ52-1
	CHPF	ENST00000691864.1		c.2062G>C	p.Glu688Gln	missense	Exon 4 of 4	ENSP00000509104.1	A0A8I5QJC8
	CHPF	ENST00000919936.1		c.2008G>C	p.Glu670Gln	missense	Exon 4 of 4	ENSP00000589995.1

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152252 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000313

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000765 AC: 19 AN: 248400 AF XY: 0.0000742

Gnomad AFR exome AF: 0.000574

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000448

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000500 AC: 73 AN: 1461248 Hom.: 0 Cov.: 30 AF XY: 0.0000481 AC XY: 35 AN XY: 726958

African (AFR) AF: 0.000269 AC: 9 AN: 33476

American (AMR) AF: 0.000112 AC: 5 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52896

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5766

European-Non Finnish (NFE) AF: 0.0000423 AC: 47 AN: 1111930

Other (OTH) AF: 0.0000497 AC: 3 AN: 60378

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152370 Hom.: 0 Cov.: 34 AF XY: 0.0000940 AC XY: 7 AN XY: 74502

African (AFR) AF: 0.000313 AC: 13 AN: 41594

American (AMR) AF: 0.000131 AC: 2 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000567

ExAC AF: 0.0000907 AC: 11

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	19
DANN	Benign	0.71
DEOGEN2	Benign	0.048	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.021	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.4	N
PhyloP100		3.3
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.060
Sift	Benign	1.0	T
Sift4G	Benign	0.48	T
Polyphen		0.0	B
Vest4		0.064
MVP		0.37
MPC		0.24
ClinPred		0.0077	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18
gMVP		0.63
Mutation Taster		=86/14	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: rs142415191; hg19: chr2-220404347; COSMIC: COSV60535493; COSMIC: COSV60535493;