rs454578

Variant names:

• chr5-81670847-G-A
• rs454578
• NM_001256732.3:c.63-20508C>T

Variant summary

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

The NM_001256732.3(SSBP2):​c.63-20508C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.753 in 151,960 control chromosomes in the GnomAD database, including 44,684 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 0.75 (44684 hom., cov: 31)
• Consequence: SSBP2 NM_001256732.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191
• Publications: 4 publications found

Genes affected

SSBP2 (HGNC:15831): (single stranded DNA binding protein 2) This gene encodes a subunit of a protein complex that interacts with single-stranded DNA and is involved in the DNA damage response and maintenance of genome stability. The encoded protein may also play a role in telomere repair. A variant of this gene may be associated with survival in human glioblastoma patients. [provided by RefSeq, Sep 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSBP2	NM_001256732.3	c.63-20508C>T		intron_variant	Intron 1 of 16	ENST00000615665.5	NP_001243661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSBP2	ENST00000615665.5	c.63-20508C>T		intron_variant	Intron 1 of 16	5	NM_001256732.3	ENSP00000483921.1

Frequencies

GnomAD3 genomes AF: 0.753 AC: 114285 AN: 151842 Hom.: 44629 Cov.: 31

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.841

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.769

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

GnomAD4 genome AF: 0.753 AC: 114388 AN: 151960 Hom.: 44684 Cov.: 31 AF XY: 0.742 AC XY: 55112 AN XY: 74252

African (AFR) AF: 0.938 AC: 38982 AN: 41540

American (AMR) AF: 0.677 AC: 10314 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.841 AC: 2921 AN: 3472

East Asian (EAS) AF: 0.299 AC: 1539 AN: 5154

South Asian (SAS) AF: 0.677 AC: 3257 AN: 4814

European-Finnish (FIN) AF: 0.571 AC: 6000 AN: 10502

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.720 AC: 48897 AN: 67920

Other (OTH) AF: 0.767 AC: 1621 AN: 2114

Alfa AF: 0.734 Hom.: 177078

Bravo AF: 0.770

Asia WGS AF: 0.521 AC: 1810 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.19
DANN	Benign	0.46
PhyloP100		-0.19
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: rs454578; hg19: chr5-80966666; COSMIC: COSV107344919;