rs149014949

Variant names:

• chr2-219539616-C-G
• rs149014949
• NM_024536.6:c.2095G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-219539616-C-G
• chr2-219539616-C-A
• chr2-219539616-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_024536.6(CHPF):​c.2095G>C​(p.Glu699Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000222 in 1,613,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. E699E) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: CHPF NM_024536.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.00
• Publications: 5 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2505492).

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.2095G>C	p.Glu699Gln	missense	Exon 4 of 4	NP_078812.3
	CHPF	NM_001195731.2		c.1609G>C	p.Glu537Gln	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.2095G>C	p.Glu699Gln	missense	Exon 4 of 4	ENSP00000243776.6	Q8IZ52-1
	CHPF	ENST00000691864.1		c.2071G>C	p.Glu691Gln	missense	Exon 4 of 4	ENSP00000509104.1	A0A8I5QJC8
	CHPF	ENST00000919936.1		c.2017G>C	p.Glu673Gln	missense	Exon 4 of 4	ENSP00000589995.1

Frequencies

GnomAD3 genomes AF: 0.0000985 AC: 15 AN: 152248 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000132 AC: 33 AN: 249868 AF XY: 0.000111

Gnomad AFR exome AF: 0.0000623

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000213

Gnomad OTH exome AF: 0.000328

GnomAD4 exome AF: 0.000235 AC: 343 AN: 1461546 Hom.: 0 Cov.: 30 AF XY: 0.000224 AC XY: 163 AN XY: 727112

African (AFR) AF: 0.0000896 AC: 3 AN: 33476

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

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

East Asian (EAS) AF: 0.000328 AC: 13 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53188

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

European-Non Finnish (NFE) AF: 0.000279 AC: 310 AN: 1111934

Other (OTH) AF: 0.000199 AC: 12 AN: 60382

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152248 Hom.: 0 Cov.: 34 AF XY: 0.0000538 AC XY: 4 AN XY: 74386

African (AFR) AF: 0.0000482 AC: 2 AN: 41468

American (AMR) AF: 0.0000654 AC: 1 AN: 15292

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

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

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

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000727 Hom.: 0

Bravo AF: 0.000151

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000989 AC: 12

EpiCase AF: 0.000109

EpiControl AF: 0.000296

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	0.15
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.092	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		6.0
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.17
Sift	Benign	0.13	T
Sift4G	Uncertain	0.018	D
Polyphen		0.98	D
Vest4		0.33
MVP		0.61
MPC		0.55
ClinPred		0.078	T
GERP RS		4.6
Varity_R		0.19
gMVP		0.45
Mutation Taster		=75/25	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: rs149014949; hg19: chr2-220404338; COSMIC: COSV60533768; COSMIC: COSV60533768;