rs2247341

Positions:

• chr4-1699590-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006527.4(SLBP):​c.453C>T​(p.Tyr151Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 1,611,414 control chromosomes in the GnomAD database, including 106,080 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 0.31 (8511 hom., cov: 32)
  • Exomes 𝑓: 0.36 (97569 hom.)
• Consequence: SLBP NM_006527.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400

Genes affected

SLBP (HGNC:10904): (stem-loop histone mRNA binding protein) This gene encodes a protein that binds to the stem-loop structure in replication-dependent histone mRNAs. Histone mRNAs do not contain introns or polyadenylation signals, and are processed by endonucleolytic cleavage. The stem-loop structure is essential for efficient processing but this structure also controls the transport, translation and stability of histone mRNAs. Expression of the protein is regulated during the cell cycle, increasing more than 10-fold during the latter part of G1. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP7: Synonymous conserved (PhyloP=-0.004 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLBP	NM_006527.4	c.453C>T	p.Tyr151Tyr	synonymous_variant	5/8	ENST00000489418.6	NP_006518.1
SLBP	NM_001306074.2	c.348C>T	p.Tyr116Tyr	synonymous_variant	4/7		NP_001293003.1
SLBP	NM_001306075.2	c.336C>T	p.Tyr112Tyr	synonymous_variant	4/7		NP_001293004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLBP	ENST00000489418.6	c.453C>T	p.Tyr151Tyr	synonymous_variant	5/8	1	NM_006527.4	ENSP00000417686.1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47484 AN: 151898 Hom.: 8510 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.319

GnomAD3 exomes AF: 0.386 AC: 97106 AN: 251270 Hom.: 20618 AF XY: 0.393 AC XY: 53427 AN XY: 135786

Gnomad AFR exome AF: 0.165

Gnomad AMR exome AF: 0.363

Gnomad ASJ exome AF: 0.353

Gnomad EAS exome AF: 0.691

Gnomad SAS exome AF: 0.490

Gnomad FIN exome AF: 0.429

Gnomad NFE exome AF: 0.343

Gnomad OTH exome AF: 0.385

GnomAD4 exome AF: 0.356 AC: 519374 AN: 1459398 Hom.: 97569 Cov.: 33 AF XY: 0.361 AC XY: 261809 AN XY: 726166

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.361

Gnomad4 ASJ exome AF: 0.352

Gnomad4 EAS exome AF: 0.698

Gnomad4 SAS exome AF: 0.484

Gnomad4 FIN exome AF: 0.428

Gnomad4 NFE exome AF: 0.335

Gnomad4 OTH exome AF: 0.363

GnomAD4 genome AF: 0.312 AC: 47504 AN: 152016 Hom.: 8511 Cov.: 32 AF XY: 0.320 AC XY: 23765 AN XY: 74284

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.692

Gnomad4 SAS AF: 0.497

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.323

Alfa AF: 0.332 Hom.: 18440

Bravo AF: 0.300

Asia WGS AF: 0.577 AC: 2005 AN: 3478

EpiCase AF: 0.341

EpiControl AF: 0.337

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	2.6
DANN	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs2247341; hg19: chr4-1701317; COSMIC: COSV59183662;