rs7675371

Positions:

• chr4-114908763-G-A
• chr4-114908763-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022569.3(NDST4):​c.1536+26443C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,044 control chromosomes in the GnomAD database, including 8,152 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 0.29 (8152 hom., cov: 32)
• Consequence: NDST4 NM_022569.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDST4	NM_022569.3	c.1536+26443C>T		intron_variant		ENST00000264363.7	NP_072091.1
NDST4	XM_017008545.3	c.399+26443C>T		intron_variant			XP_016864034.1
NDST4	XM_017008546.2	c.399+26443C>T		intron_variant			XP_016864035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDST4	ENST00000264363.7	c.1536+26443C>T		intron_variant		1	NM_022569.3	ENSP00000264363	P1
NDST4	ENST00000504854.1	c.399+26443C>T		intron_variant, NMD_transcript_variant		1		ENSP00000423218
NDST4	ENST00000613194.4	c.399+26443C>T		intron_variant		5		ENSP00000483949

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43589 AN: 151926 Hom.: 8128 Cov.: 32

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.287 AC: 43666 AN: 152044 Hom.: 8152 Cov.: 32 AF XY: 0.296 AC XY: 21967 AN XY: 74310

Gnomad4 AFR AF: 0.527

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.267

Alfa AF: 0.174 Hom.: 4733

Bravo AF: 0.288

Asia WGS AF: 0.325 AC: 1122 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.97
DANN	Benign	0.45

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

LitVar

Other links and lift over

dbSNP: rs7675371; hg19: chr4-115829919;