chr1-86949675-T-C

Variant names:

• chr1-86949675-T-C
• rs1199724
• NM_012262.4:c.124+34515T>C

Variant summary

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

The NM_012262.4(HS2ST1):​c.124+34515T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.971 in 152,358 control chromosomes in the GnomAD database, including 71,843 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 0.97 (71843 hom., cov: 32)
• Consequence: HS2ST1 NM_012262.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129
• Publications: 1 publications found

Genes affected

HS2ST1 (HGNC:5193): (heparan sulfate 2-O-sulfotransferase 1) Heparan sulfate biosynthetic enzymes are key components in generating a myriad of distinct heparan sulfate fine structures that carry out multiple biologic activities. This gene encodes a member of the heparan sulfate biosynthetic enzyme family that transfers sulfate to the 2 position of the iduronic acid residue of heparan sulfate. The disruption of this gene resulted in no kidney formation in knockout embryonic mice, indicating that the absence of this enzyme may interfere with the signaling required for kidney formation. Two alternatively spliced transcript variants that encode different proteins have been found for this gene. [provided by RefSeq, Aug 2008]

HS2ST1 Gene-Disease associations (from GenCC):

• neurofacioskeletal syndrome with or without renal agenesis

  Inheritance: Unknown, AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.984 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012262.4. 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
	HS2ST1	NM_012262.4	MANE Select	c.124+34515T>C		intron	N/A	NP_036394.1	Q7LGA3-1
	HS2ST1	NM_001134492.2		c.124+34515T>C		intron	N/A	NP_001127964.1	Q7LGA3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS2ST1	ENST00000370550.10	TSL:1 MANE Select	c.124+34515T>C		intron	N/A	ENSP00000359581.4	Q7LGA3-1
	HS2ST1	ENST00000370551.8	TSL:1	c.124+34515T>C		intron	N/A	ENSP00000359582.3	Q7LGA3-3
	HS2ST1	ENST00000690674.1		c.-51+33876T>C		intron	N/A	ENSP00000509377.1	A0A8I5KW95

Frequencies

GnomAD3 genomes AF: 0.971 AC: 147812 AN: 152240 Hom.: 71786 Cov.: 32

Gnomad AFR AF: 0.992

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.958

Gnomad ASJ AF: 0.924

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.992

Gnomad FIN AF: 0.985

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.958

Gnomad OTH AF: 0.964

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

GnomAD4 genome AF: 0.971 AC: 147928 AN: 152358 Hom.: 71843 Cov.: 32 AF XY: 0.973 AC XY: 72478 AN XY: 74500

African (AFR) AF: 0.992 AC: 41238 AN: 41584

American (AMR) AF: 0.958 AC: 14659 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.924 AC: 3208 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5179 AN: 5180

South Asian (SAS) AF: 0.991 AC: 4786 AN: 4830

European-Finnish (FIN) AF: 0.985 AC: 10467 AN: 10630

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.958 AC: 65161 AN: 68042

Other (OTH) AF: 0.964 AC: 2038 AN: 2114

Alfa AF: 0.966 Hom.: 18786

Bravo AF: 0.970

Asia WGS AF: 0.995 AC: 3459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.7
DANN	Benign	0.39
PhyloP100		0.13
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: rs1199724; hg19: chr1-87415358;