NM_006527.4:c.281+781A>C

Variant names:

• chr4-1702815-T-G
• rs2236995
• NM_006527.4:c.281+781A>C

Variant summary

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

The NM_006527.4(SLBP):​c.281+781A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 152,026 control chromosomes in the GnomAD database, including 16,232 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 0.44 (16232 hom., cov: 32)
• Consequence: SLBP NM_006527.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.507
• Publications: 20 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLBP	NM_006527.4	MANE Select	c.281+781A>C		intron	N/A	NP_006518.1
	SLBP	NM_001306074.2		c.177-2745A>C		intron	N/A	NP_001293003.1
	SLBP	NM_001306075.2		c.164+781A>C		intron	N/A	NP_001293004.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLBP	ENST00000489418.6	TSL:1 MANE Select	c.281+781A>C		intron	N/A	ENSP00000417686.1
	SLBP	ENST00000318386.8	TSL:3	c.281+781A>C		intron	N/A	ENSP00000316490.4
	SLBP	ENST00000904664.1		c.281+781A>C		intron	N/A	ENSP00000574723.1

Frequencies

GnomAD3 genomes AF: 0.441 AC: 66951 AN: 151910 Hom.: 16220 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.441 AC: 67000 AN: 152026 Hom.: 16232 Cov.: 32 AF XY: 0.443 AC XY: 32882 AN XY: 74306

African (AFR) AF: 0.242 AC: 10042 AN: 41484

American (AMR) AF: 0.442 AC: 6746 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 1951 AN: 3470

East Asian (EAS) AF: 0.695 AC: 3594 AN: 5170

South Asian (SAS) AF: 0.593 AC: 2855 AN: 4816

European-Finnish (FIN) AF: 0.490 AC: 5182 AN: 10566

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.515 AC: 34980 AN: 67942

Other (OTH) AF: 0.452 AC: 952 AN: 2108

Alfa AF: 0.488 Hom.: 8902

Bravo AF: 0.430

Asia WGS AF: 0.621 AC: 2161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.99
DANN	Benign	0.42
PhyloP100		-0.51
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: rs2236995; hg19: chr4-1704542;