chr15-101177475-G-T

Variant names:

• chr15-101177475-G-T
• rs8024370
• NM_014918.5:c.2322C>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014918.5(CHSY1):​c.2322C>A​(p.Thr774Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 1,613,236 control chromosomes in the GnomAD database, including 299,583 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (35972 hom., cov: 33)
  • Exomes 𝑓: 0.60 (263611 hom.)
• Consequence: CHSY1 NM_014918.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.19
• Publications: 20 publications found

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 15-101177475-G-T is Benign according to our data. Variant chr15-101177475-G-T is described in ClinVar as Benign. ClinVar VariationId is 672053.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.19 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.859 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.2322C>A	p.Thr774Thr	synonymous	Exon 3 of 3	NP_055733.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHSY1	ENST00000254190.4	TSL:1 MANE Select	c.2322C>A	p.Thr774Thr	synonymous	Exon 3 of 3	ENSP00000254190.3	Q86X52
	CHSY1	ENST00000968149.1		c.2316C>A	p.Thr772Thr	synonymous	Exon 3 of 3	ENSP00000638208.1
	CHSY1	ENST00000543813.2	TSL:2	n.*1637C>A		non_coding_transcript_exon	Exon 3 of 3	ENSP00000496160.1	A0A2R8Y7B7

Frequencies

GnomAD3 genomes AF: 0.676 AC: 102715 AN: 152026 Hom.: 35928 Cov.: 33

Gnomad AFR AF: 0.859

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.881

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.655

GnomAD2 exomes AF: 0.646 AC: 162025 AN: 250676 AF XY: 0.640

Gnomad AFR exome AF: 0.869

Gnomad AMR exome AF: 0.675

Gnomad ASJ exome AF: 0.534

Gnomad EAS exome AF: 0.878

Gnomad FIN exome AF: 0.640

Gnomad NFE exome AF: 0.569

Gnomad OTH exome AF: 0.625

GnomAD4 exome AF: 0.595 AC: 869586 AN: 1461092 Hom.: 263611 Cov.: 53 AF XY: 0.597 AC XY: 433587 AN XY: 726798

African (AFR) AF: 0.871 AC: 29141 AN: 33446

American (AMR) AF: 0.675 AC: 30088 AN: 44606

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 14105 AN: 26112

East Asian (EAS) AF: 0.897 AC: 35607 AN: 39696

South Asian (SAS) AF: 0.686 AC: 59110 AN: 86104

European-Finnish (FIN) AF: 0.634 AC: 33846 AN: 53416

Middle Eastern (MID) AF: 0.624 AC: 3593 AN: 5760

European-Non Finnish (NFE) AF: 0.564 AC: 626827 AN: 1111592

Other (OTH) AF: 0.617 AC: 37269 AN: 60360

GnomAD4 genome AF: 0.676 AC: 102811 AN: 152144 Hom.: 35972 Cov.: 33 AF XY: 0.683 AC XY: 50798 AN XY: 74342

African (AFR) AF: 0.859 AC: 35678 AN: 41530

American (AMR) AF: 0.671 AC: 10259 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1795 AN: 3470

East Asian (EAS) AF: 0.881 AC: 4561 AN: 5180

South Asian (SAS) AF: 0.695 AC: 3355 AN: 4826

European-Finnish (FIN) AF: 0.644 AC: 6793 AN: 10548

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38312 AN: 67978

Other (OTH) AF: 0.654 AC: 1381 AN: 2112

Alfa AF: 0.612 Hom.: 17877

Bravo AF: 0.685

Asia WGS AF: 0.779 AC: 2705 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	Temtamy preaxial brachydactyly syndrome (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.17
DANN	Benign	0.47
PhyloP100		-1.2
Mutation Taster		=98/2	polymorphism (auto)

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: rs8024370; hg19: chr15-101717680; COSMIC: COSV54253326; COSMIC: COSV54253326;