rs7770227

Variant names:

• chr6-114301050-G-A
• rs7770227
• NM_153612.4:c.-339+41145C>T

Variant summary

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

The NM_153612.4(HS3ST5):​c.-339+41145C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 151,942 control chromosomes in the GnomAD database, including 9,097 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 0.33 (9097 hom., cov: 32)
• Consequence: HS3ST5 NM_153612.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263
• Publications: 4 publications found

Genes affected

HS3ST5 (HGNC:19419): (heparan sulfate-glucosamine 3-sulfotransferase 5) HS3ST5 belongs to a group of heparan sulfate 3-O-sulfotransferases (EC 2.8.2.23) that transfer sulfate from 3-prime-phosphoadenosine 5-prime phosphosulfate (PAPS) to heparan sulfate and heparin (Mochizuki et al., 2003 [PubMed 12740361]).[supplied by OMIM, Mar 2008]

HDAC2-AS2 (HGNC:43590): (HDAC2 and HS3ST5 antisense RNA 2)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS3ST5	NM_153612.4	c.-339+41145C>T		intron_variant	Intron 1 of 4	ENST00000312719.10	NP_705840.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HS3ST5	ENST00000312719.10	c.-339+41145C>T		intron_variant	Intron 1 of 4	2	NM_153612.4	ENSP00000427888.1
HDAC2-AS2	ENST00000519104.5	n.1800-39472G>A		intron_variant	Intron 9 of 9	1
HDAC2-AS2	ENST00000518470.5	n.197+19042G>A		intron_variant	Intron 1 of 5	4

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50344 AN: 151824 Hom.: 9104 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.331 AC: 50336 AN: 151942 Hom.: 9097 Cov.: 32 AF XY: 0.329 AC XY: 24444 AN XY: 74270

African (AFR) AF: 0.212 AC: 8777 AN: 41446

American (AMR) AF: 0.269 AC: 4099 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1188 AN: 3466

East Asian (EAS) AF: 0.153 AC: 788 AN: 5158

South Asian (SAS) AF: 0.359 AC: 1724 AN: 4806

European-Finnish (FIN) AF: 0.401 AC: 4232 AN: 10558

Middle Eastern (MID) AF: 0.387 AC: 113 AN: 292

European-Non Finnish (NFE) AF: 0.415 AC: 28169 AN: 67932

Other (OTH) AF: 0.340 AC: 718 AN: 2110

Alfa AF: 0.385 Hom.: 18981

Bravo AF: 0.314

Asia WGS AF: 0.242 AC: 844 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.71
DANN	Benign	0.54
PhyloP100		-0.26
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: rs7770227; hg19: chr6-114622214;