NM_130468.4:c.-27C>G

Variant names:

• chr15-40471187-C-G
• rs1555410680
• NM_130468.4:c.-27C>G

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.-27C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000856 in 1,168,890 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 8.6e-7 (0 hom.)
• Consequence: CHST14 NM_130468.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.118
• 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 15-40471187-C-G is Benign according to our data. Variant chr15-40471187-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 511518.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.-27C>G		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.-27C>G		5_prime_UTR	Exon 1 of 1	ENSP00000307297.6	Q8NCH0
	CHST14	ENST00000559991.1	TSL:5	c.-27C>G		5_prime_UTR	Exon 1 of 2	ENSP00000453882.1	H0YN65
	ENSG00000302612	ENST00000788112.1		n.151+468G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.56e-7 AC: 1 AN: 1168890 Hom.: 0 Cov.: 29 AF XY: 0.00000177 AC XY: 1 AN XY: 564540

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 22798

American (AMR) AF: 0.00 AC: 0 AN: 9016

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15724

East Asian (EAS) AF: 0.00 AC: 0 AN: 26752

South Asian (SAS) AF: 0.0000220 AC: 1 AN: 45558

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27862

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3262

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 970004

Other (OTH) AF: 0.00 AC: 0 AN: 47914

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	8.1
DANN	Benign	0.70
PhyloP100		-0.12
PromoterAI		-0.012	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: rs1555410680; hg19: chr15-40763386;