2-20618791-G-C

Position:

• chr2-20618791-G-C

Variant summary

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

The ENST00000304031.8(HS1BP3):​c.*196C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0481 in 1,392,082 control chromosomes in the GnomAD database, including 1,867 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 0.037 (157 hom., cov: 33)
  • Exomes 𝑓: 0.049 (1710 hom.)
• Consequence: HS1BP3 ENST00000304031.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412

Genes affected

HS1BP3 (HGNC:24979): (HCLS1 binding protein 3) The protein encoded by this gene shares similarity with mouse Hs1bp3, an Hcls1/Hs1-interacting protein that may be involved in lymphocyte activation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HS1BP3	NM_022460.4	c.*196C>G		3_prime_UTR_variant	7/7	ENST00000304031.8	NP_071905.3
HS1BP3	XM_017004696.3	c.920+5105C>G		intron_variant			XP_016860185.1
HS1BP3	XM_017004697.3	c.920+5105C>G		intron_variant			XP_016860186.1
HS1BP3	XM_017004698.2	c.920+5105C>G		intron_variant			XP_016860187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HS1BP3	ENST00000304031.8	c.*196C>G		3_prime_UTR_variant	7/7	1	NM_022460.4	ENSP00000305193	P1
HS1BP3	ENST00000415264.5	c.178+5105C>G		intron_variant		3		ENSP00000387364
HS1BP3	ENST00000446825.1	c.302+5105C>G		intron_variant		3		ENSP00000389960
HS1BP3	ENST00000651498.1	c.*816C>G		3_prime_UTR_variant, NMD_transcript_variant	6/6			ENSP00000498575

Frequencies

GnomAD3 genomes AF: 0.0371 AC: 5644 AN: 152130 Hom.: 157 Cov.: 33

Gnomad AFR AF: 0.00929

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0303

Gnomad ASJ AF: 0.0628

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00849

Gnomad FIN AF: 0.0675

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0544

Gnomad OTH AF: 0.0359

GnomAD4 exome AF: 0.0495 AC: 61346 AN: 1239834 Hom.: 1710 Cov.: 34 AF XY: 0.0494 AC XY: 29488 AN XY: 597246

Gnomad4 AFR exome AF: 0.00727

Gnomad4 AMR exome AF: 0.0267

Gnomad4 ASJ exome AF: 0.0501

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00954

Gnomad4 FIN exome AF: 0.0575

Gnomad4 NFE exome AF: 0.0550

Gnomad4 OTH exome AF: 0.0416

GnomAD4 genome AF: 0.0371 AC: 5643 AN: 152248 Hom.: 157 Cov.: 33 AF XY: 0.0369 AC XY: 2751 AN XY: 74456

Gnomad4 AFR AF: 0.00926

Gnomad4 AMR AF: 0.0303

Gnomad4 ASJ AF: 0.0628

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00871

Gnomad4 FIN AF: 0.0675

Gnomad4 NFE AF: 0.0544

Gnomad4 OTH AF: 0.0355

Alfa AF: 0.0191 Hom.: 5

Bravo AF: 0.0335

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.94
DANN	Benign	0.46

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: rs11680700; hg19: chr2-20818551;