dbSNP rs3803422: CHSY1:p.Val604Val (chr15-101177985-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_014918.5(CHSY1):c.1812G>A(p.Val604Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0154 in 1,614,176 control chromosomes in the GnomAD database, including 335 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 31 hom., cov: 33)

Exomes 𝑓: 0.015 ( 304 hom. )

Consequence

CHSY1
NM_014918.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.25

Publications

5 publications found

Variant links:

Genes affected

CHSY1 (HGNC:17198): (chondroitin sulfate synthase 1) This gene encodes a member of the chondroitin N-acetylgalactosaminyltransferase family. These enzymes possess dual glucuronyltransferase and galactosaminyltransferase activity and play critical roles in the biosynthesis of chondroitin sulfate, a glycosaminoglycan involved in many biological processes including cell proliferation and morphogenesis. Decreased expression of this gene may play a role in colorectal cancer, and mutations in this gene are a cause of temtamy preaxial brachydactyly syndrome. [provided by RefSeq, Dec 2011]

CHSY1 Gene-Disease associations (from GenCC):

temtamy preaxial brachydactyly syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet

CHSY1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 15-101177985-C-T is Benign according to our data. Variant chr15-101177985-C-T is described in ClinVar as Benign. ClinVar VariationId is 466170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.25 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0627 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014918.5. 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
	CHSY1	NM_014918.5	MANE Select	c.1812G>A	p.Val604Val	synonymous	Exon 3 of 3	NP_055733.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHSY1	ENST00000254190.4	TSL:1 MANE Select	c.1812G>A	p.Val604Val	synonymous	Exon 3 of 3	ENSP00000254190.3	Q86X52
CHSY1	ENST00000968149.1		c.1806G>A	p.Val602Val	synonymous	Exon 3 of 3	ENSP00000638208.1
CHSY1	ENST00000543813.2	TSL:2	n.*1127G>A		non_coding_transcript_exon	Exon 3 of 3	ENSP00000496160.1	A0A2R8Y7B7

Frequencies

GnomAD3 genomes

AF:

0.0162

AC:

2459

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00579

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0351

Gnomad ASJ

AF:

0.0256

Gnomad EAS

AF:

0.0690

Gnomad SAS

AF:

0.0166

Gnomad FIN

AF:

0.0264

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0122

Gnomad OTH

AF:

0.0168

GnomAD2 exomes

AF:

0.0242

AC:

6094

AN:

251438

AF XY:

0.0224

show subpopulations

Gnomad AFR exome

AF:

0.00406

Gnomad AMR exome

AF:

0.0551

Gnomad ASJ exome

AF:

0.0317

Gnomad EAS exome

AF:

0.0708

Gnomad FIN exome

AF:

0.0276

Gnomad NFE exome

AF:

0.0122

Gnomad OTH exome

AF:

0.0235

GnomAD4 exome

AF:

0.0153

AC:

22323

AN:

1461862

Hom.:

304

Cov.:

AF XY:

0.0150

AC XY:

10877

AN XY:

727226

show subpopulations

African (AFR)

AF:

0.00406

AC:

136

AN:

33480

American (AMR)

AF:

0.0541

AC:

2419

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0308

AC:

804

AN:

26132

East Asian (EAS)

AF:

0.0566

AC:

2247

AN:

39700

South Asian (SAS)

AF:

0.0123

AC:

1065

AN:

86256

European-Finnish (FIN)

AF:

0.0274

AC:

1461

AN:

53418

Middle Eastern (MID)

AF:

0.0113

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0117

AC:

13024

AN:

1111992

Other (OTH)

AF:

0.0182

AC:

1102

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

1411

2821

4232

5642

7053

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

550

1100

1650

2200

2750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0162

AC:

2463

AN:

152314

Hom.:

Cov.:

AF XY:

0.0173

AC XY:

1286

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00587

AC:

244

AN:

41564

American (AMR)

AF:

0.0352

AC:

539

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0256

AC:

AN:

3472

East Asian (EAS)

AF:

0.0685

AC:

355

AN:

5180

South Asian (SAS)

AF:

0.0168

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0264

AC:

280

AN:

10618

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0122

AC:

833

AN:

68036

Other (OTH)

AF:

0.0175

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

116

232

347

463

579

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0150

Hom.:

Bravo

AF:

0.0168

Asia WGS

AF:

0.0360

AC:

123

AN:

3478

EpiCase

AF:

0.0130

EpiControl

AF:

0.0113

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Temtamy preaxial brachydactyly syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

9.2

(source)

DANN

Benign

0.85

PhyloP100

1.2

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over