rs1057523825

Variant names:

• chr15-40471209-G-A
• rs1057523825
• NM_130468.4:c.-5G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_130468.4(CHST14):​c.-5G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHST14 NM_130468.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.58
• Publications: 0 publications found

Genes affected

CHST14 (HGNC:24464): (carbohydrate sulfotransferase 14) This gene encodes a member of the HNK-1 family of sulfotransferases. The encoded protein transfers sulfate to the C-4 hydroxyl of N-acetylgalactosamine residues in dermatan sulfate. Mutations in this gene have been associated with adducted thumb-clubfoot syndrome.[provided by RefSeq, Mar 2010]

CHST14 Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome, musculocontractural type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
• Ehlers-Danlos syndrome, musculocontractural type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000302612 (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 15-40471209-G-A is Benign according to our data. Variant chr15-40471209-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 390588.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130468.4. 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
	CHST14	NM_130468.4	MANE Select	c.-5G>A		5_prime_UTR	Exon 1 of 1	NP_569735.1	Q8NCH0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST14	ENST00000306243.7	TSL:6 MANE Select	c.-5G>A		5_prime_UTR	Exon 1 of 1	ENSP00000307297.6	Q8NCH0
	CHST14	ENST00000559991.1	TSL:5	c.-5G>A		5_prime_UTR	Exon 1 of 2	ENSP00000453882.1	H0YN65
	ENSG00000302612	ENST00000788112.1		n.151+446C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1236768 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 603888

African (AFR) AF: 0.00 AC: 0 AN: 23716

American (AMR) AF: 0.00 AC: 0 AN: 12190

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17112

East Asian (EAS) AF: 0.00 AC: 0 AN: 28844

South Asian (SAS) AF: 0.00 AC: 0 AN: 56672

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30000

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3484

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1013996

Other (OTH) AF: 0.00 AC: 0 AN: 50754

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	16
DANN	Benign	0.89
PhyloP100		1.6
PromoterAI		-0.0098	Neutral

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: rs1057523825; hg19: chr15-40763408;