chr4-1699590-G-A

Variant names:

• chr4-1699590-G-A
• rs2247341
• NM_006527.4:c.453C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4 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
• Publications: 81 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.257).
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006527.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLBP	NM_006527.4	MANE Select	c.453C>T	p.Tyr151Tyr	synonymous	Exon 5 of 8	NP_006518.1
	SLBP	NM_001306074.2		c.348C>T	p.Tyr116Tyr	synonymous	Exon 4 of 7	NP_001293003.1
	SLBP	NM_001306075.2		c.336C>T	p.Tyr112Tyr	synonymous	Exon 4 of 7	NP_001293004.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLBP	ENST00000489418.6	TSL:1 MANE Select	c.453C>T	p.Tyr151Tyr	synonymous	Exon 5 of 8	ENSP00000417686.1
	SLBP	ENST00000318386.8	TSL:3	c.474C>T	p.Tyr158Tyr	synonymous	Exon 5 of 8	ENSP00000316490.4
	SLBP	ENST00000488267.5	TSL:2	c.348C>T	p.Tyr116Tyr	synonymous	Exon 4 of 7	ENSP00000418658.1

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

GnomAD2 exomes AF: 0.386 AC: 97106 AN: 251270 AF XY: 0.393

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 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

African (AFR) AF: 0.165 AC: 5508 AN: 33466

American (AMR) AF: 0.361 AC: 16130 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 9181 AN: 26116

East Asian (EAS) AF: 0.698 AC: 27669 AN: 39666

South Asian (SAS) AF: 0.484 AC: 41743 AN: 86200

European-Finnish (FIN) AF: 0.428 AC: 22818 AN: 53372

Middle Eastern (MID) AF: 0.378 AC: 2176 AN: 5760

European-Non Finnish (NFE) AF: 0.335 AC: 372283 AN: 1109796

Other (OTH) AF: 0.363 AC: 21866 AN: 60304

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

African (AFR) AF: 0.171 AC: 7077 AN: 41478

American (AMR) AF: 0.322 AC: 4913 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1244 AN: 3472

East Asian (EAS) AF: 0.692 AC: 3575 AN: 5164

South Asian (SAS) AF: 0.497 AC: 2395 AN: 4822

European-Finnish (FIN) AF: 0.422 AC: 4444 AN: 10530

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.335 AC: 22789 AN: 67964

Other (OTH) AF: 0.323 AC: 680 AN: 2108

Alfa AF: 0.331 Hom.: 37504

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	2.6
DANN	Benign	0.55
PhyloP100		-0.0040
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	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: rs2247341; hg19: chr4-1701317; COSMIC: COSV59183662;