rs2077119

Variant names:

• chr3-186612673-T-G
• rs2077119
• ENST00000625386.2:n.388+29281A>C

Variant summary

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

The ENST00000840331.1(HRG-AS1):​n.175-6364A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 152,100 control chromosomes in the GnomAD database, including 11,284 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 0.35 (11284 hom., cov: 31)
• Consequence: HRG-AS1 ENST00000840331.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.571
• Publications: 15 publications found

Genes affected

HRG-AS1 (HGNC:55915): (HRG and FETUB antisense RNA 1)

AHSG (HGNC:349): (alpha 2-HS glycoprotein) The protein encoded by this gene is a negatively-charged serum glycoprotein that is synthesized by hepatocytes. The encoded protein consists of two polypeptide chains, which are both cleaved from a proprotein encoded from a single mRNA. It is involved in several processes, including endocytosis, brain development, and the formation of bone tissue. Defects in this gene are a cause of susceptibility to leanness. [provided by RefSeq, Aug 2017]

AHSG Gene-Disease associations (from GenCC):

• alopecia-intellectual disability syndrome 1

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000840331.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HRG-AS1	ENST00000625386.2	TSL:5	n.388+29281A>C		intron	N/A
	HRG-AS1	ENST00000628505.2	TSL:5	n.390-6364A>C		intron	N/A
	HRG-AS1	ENST00000630178.2	TSL:5	n.239-32707A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52922 AN: 151982 Hom.: 11283 Cov.: 31

Gnomad AFR AF: 0.0938

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.348 AC: 52934 AN: 152100 Hom.: 11284 Cov.: 31 AF XY: 0.350 AC XY: 26019 AN XY: 74328

African (AFR) AF: 0.0937 AC: 3890 AN: 41530

American (AMR) AF: 0.377 AC: 5763 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1672 AN: 3470

East Asian (EAS) AF: 0.598 AC: 3084 AN: 5160

South Asian (SAS) AF: 0.504 AC: 2426 AN: 4816

European-Finnish (FIN) AF: 0.349 AC: 3690 AN: 10564

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31027 AN: 67966

Other (OTH) AF: 0.392 AC: 828 AN: 2110

Alfa AF: 0.401 Hom.: 21691

Bravo AF: 0.340

Asia WGS AF: 0.492 AC: 1711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.44
DANN	Benign	0.69
PhyloP100		-0.57
PromoterAI		-0.00060	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2077119;

hg19: chr3-186330462;