rs3827733

Variant names:

• chr1-113795967-A-G
• rs3827733
• NM_018364.5:c.1377+1396T>C

Variant summary

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

The NM_018364.5(RSBN1):​c.1377+1396T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,074 control chromosomes in the GnomAD database, including 2,127 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 0.16 (2127 hom., cov: 32)
• Consequence: RSBN1 NM_018364.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• Publications: 14 publications found

Genes affected

RSBN1 (HGNC:25642): (round spermatid basic protein 1) Predicted to enable dioxygenase activity and metal ion binding activity. Predicted to be involved in chromatin organization. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSBN1	NM_018364.5	c.1377+1396T>C		intron_variant	Intron 2 of 6	ENST00000261441.9	NP_060834.2
RSBN1	XM_017001518.3	c.*334T>C		3_prime_UTR_variant	Exon 3 of 3		XP_016857007.1
RSBN1	NR_130896.2	n.1559+219T>C		intron_variant	Intron 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSBN1	ENST00000261441.9	c.1377+1396T>C		intron_variant	Intron 2 of 6	2	NM_018364.5	ENSP00000261441.5
RSBN1	ENST00000612242.4	c.1377+1396T>C		intron_variant	Intron 2 of 6	2		ENSP00000479490.1
RSBN1	ENST00000615321.1	c.1233+1396T>C		intron_variant	Intron 2 of 6	2		ENSP00000480408.1
RSBN1	ENST00000476412.5	n.*115+219T>C		intron_variant	Intron 3 of 7	2		ENSP00000433256.2

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23791 AN: 151956 Hom.: 2127 Cov.: 32

Gnomad AFR AF: 0.0819

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.157 AC: 23802 AN: 152074 Hom.: 2127 Cov.: 32 AF XY: 0.157 AC XY: 11701 AN XY: 74354

African (AFR) AF: 0.0819 AC: 3399 AN: 41510

American (AMR) AF: 0.166 AC: 2542 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 522 AN: 3468

East Asian (EAS) AF: 0.229 AC: 1185 AN: 5176

South Asian (SAS) AF: 0.117 AC: 566 AN: 4826

European-Finnish (FIN) AF: 0.199 AC: 2108 AN: 10574

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12858 AN: 67942

Other (OTH) AF: 0.165 AC: 347 AN: 2104

Alfa AF: 0.177 Hom.: 1577

Bravo AF: 0.153

Asia WGS AF: 0.190 AC: 662 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	13
DANN	Benign	0.75
PhyloP100		1.2
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: rs3827733; hg19: chr1-114338589; COSMIC: COSV54731608;