4-114997028-T-C

Variant names:

• chr4-114997028-T-C
• rs2583513
• NM_022569.3:c.979-19754A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022569.3(NDST4):​c.979-19754A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 151,866 control chromosomes in the GnomAD database, including 13,784 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (13784 hom., cov: 32)
• Consequence: NDST4 NM_022569.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225
• Publications: 2 publications found

Genes affected

NDST4 (HGNC:20779): (N-deacetylase and N-sulfotransferase 4) Predicted to enable [heparan sulfate]-glucosamine N-sulfotransferase activity and deacetylase activity. Predicted to be involved in heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process. Predicted to be located in Golgi membrane. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022569.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDST4	NM_022569.3	MANE Select	c.979-19754A>G		intron	N/A	NP_072091.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDST4	ENST00000264363.7	TSL:1 MANE Select	c.979-19754A>G		intron	N/A	ENSP00000264363.2
	NDST4	ENST00000504854.1	TSL:1	n.-71-26444A>G		intron	N/A	ENSP00000423218.1
	NDST4	ENST00000613194.4	TSL:5	c.-159-19754A>G		intron	N/A	ENSP00000483949.1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62180 AN: 151746 Hom.: 13765 Cov.: 32

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.447

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.410 AC: 62253 AN: 151866 Hom.: 13784 Cov.: 32 AF XY: 0.414 AC XY: 30701 AN XY: 74238

African (AFR) AF: 0.582 AC: 24107 AN: 41420

American (AMR) AF: 0.369 AC: 5611 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1707 AN: 3464

East Asian (EAS) AF: 0.418 AC: 2154 AN: 5150

South Asian (SAS) AF: 0.493 AC: 2371 AN: 4806

European-Finnish (FIN) AF: 0.305 AC: 3226 AN: 10570

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21676 AN: 67932

Other (OTH) AF: 0.448 AC: 943 AN: 2106

Alfa AF: 0.354 Hom.: 2577

Bravo AF: 0.415

Asia WGS AF: 0.451 AC: 1571 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.36
PhyloP100		0.23
Mutation Taster		=100/0	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: rs2583513; hg19: chr4-115918184;