2-20619004-C-T

Variant names:

• chr2-20619004-C-T
• rs3732149
• NM_022460.4:c.1162G>A

Variant summary

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

The NM_022460.4(HS1BP3):​c.1162G>A​(p.Ala388Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 1,613,200 control chromosomes in the GnomAD database, including 34,443 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.18 (2578 hom., cov: 33)
  • Exomes 𝑓: 0.21 (31865 hom.)
• Consequence: HS1BP3 NM_022460.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54

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 (MetaRNN=0.0036723316).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS1BP3	NM_022460.4	c.1162G>A	p.Ala388Thr	missense_variant	Exon 7 of 7	ENST00000304031.8	NP_071905.3
HS1BP3	XM_017004696.3	c.920+4892G>A		intron_variant	Intron 6 of 7		XP_016860185.1
HS1BP3	XM_017004697.3	c.920+4892G>A		intron_variant	Intron 6 of 7		XP_016860186.1
HS1BP3	XM_017004698.2	c.920+4892G>A		intron_variant	Intron 6 of 7		XP_016860187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HS1BP3	ENST00000304031.8	c.1162G>A	p.Ala388Thr	missense_variant	Exon 7 of 7	1	NM_022460.4	ENSP00000305193.3

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26777 AN: 151976 Hom.: 2575 Cov.: 33

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.0847

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.173

GnomAD3 exomes AF: 0.183 AC: 45529 AN: 249440 Hom.: 4372 AF XY: 0.186 AC XY: 25129 AN XY: 134964

Gnomad AFR exome AF: 0.132

Gnomad AMR exome AF: 0.141

Gnomad ASJ exome AF: 0.184

Gnomad EAS exome AF: 0.0894

Gnomad SAS exome AF: 0.204

Gnomad FIN exome AF: 0.180

Gnomad NFE exome AF: 0.212

Gnomad OTH exome AF: 0.181

GnomAD4 exome AF: 0.205 AC: 299923 AN: 1461106 Hom.: 31865 Cov.: 37 AF XY: 0.206 AC XY: 149866 AN XY: 726854

Gnomad4 AFR exome AF: 0.134

Gnomad4 AMR exome AF: 0.142

Gnomad4 ASJ exome AF: 0.188

Gnomad4 EAS exome AF: 0.0836

Gnomad4 SAS exome AF: 0.202

Gnomad4 FIN exome AF: 0.180

Gnomad4 NFE exome AF: 0.217

Gnomad4 OTH exome AF: 0.189

GnomAD4 genome AF: 0.176 AC: 26779 AN: 152094 Hom.: 2578 Cov.: 33 AF XY: 0.175 AC XY: 13011 AN XY: 74362

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.0845

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.172

Alfa AF: 0.200 Hom.: 5137

Bravo AF: 0.171

TwinsUK AF: 0.221 AC: 820

ALSPAC AF: 0.221 AC: 852

ESP6500AA AF: 0.139 AC: 611

ESP6500EA AF: 0.208 AC: 1793

ExAC AF: 0.183 AC: 22176

Asia WGS AF: 0.129 AC: 448 AN: 3478

EpiCase AF: 0.214

EpiControl AF: 0.213

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.015
DANN	Benign	0.66
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.46	T
MetaRNN	Benign	0.0037	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.48	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.043
Sift	Benign	0.65	T
Sift4G	Benign	0.20	T
Polyphen		0.0080	B
Vest4		0.0050
MPC		0.13
ClinPred		0.00059	T
GERP RS		-1.7
Varity_R		0.029
gMVP		0.090

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: rs3732149; hg19: chr2-20818764; COSMIC: COSV58315236; COSMIC: COSV58315236;