rs2930961

Positions:

• chr8-94431578-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001256141.2(FSBP):​c.*553A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 931,360 control chromosomes in the GnomAD database, including 49,560 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 0.36 (9870 hom., cov: 32)
  • Exomes 𝑓: 0.32 (39690 hom.)
• Consequence: FSBP NM_001256141.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.57

Genes affected

FSBP (HGNC:43653): (fibrinogen silencer binding protein) Enables identical protein binding activity. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RAD54B (HGNC:17228): (RAD54 homolog B) The protein encoded by this gene belongs to the DEAD-like helicase superfamily. It shares similarity with Saccharomyces cerevisiae RAD54 and RDH54, both of which are involved in homologous recombination and repair of DNA. This protein binds to double-stranded DNA, and displays ATPase activity in the presence of DNA. This gene is highly expressed in testis and spleen, which suggests active roles in meiotic and mitotic recombination. Homozygous mutations of this gene were observed in primary lymphoma and colon cancer. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FSBP	NM_001256141.2	c.*553A>G		3_prime_UTR_variant	2/2	ENST00000481490.3	NP_001243070.1
RAD54B	NM_012415.3	c.305-20263A>G		intron_variant		ENST00000336148.10	NP_036547.1
RAD54B	NM_001205262.3	c.*1029A>G		3_prime_UTR_variant	4/4		NP_001192191.1
RAD54B	NM_001205263.2	c.-249+4917A>G		intron_variant			NP_001192192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FSBP	ENST00000481490	c.*553A>G		3_prime_UTR_variant	2/2	1	NM_001256141.2	ENSP00000420405.2
RAD54B	ENST00000336148.10	c.305-20263A>G		intron_variant		1	NM_012415.3	ENSP00000336606.5

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54042 AN: 151818 Hom.: 9869 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.376

GnomAD4 exome AF: 0.317 AC: 247384 AN: 779422 Hom.: 39690 Cov.: 12 AF XY: 0.317 AC XY: 114688 AN XY: 361286

Gnomad4 AFR exome AF: 0.345

Gnomad4 AMR exome AF: 0.523

Gnomad4 ASJ exome AF: 0.335

Gnomad4 EAS exome AF: 0.468

Gnomad4 SAS exome AF: 0.399

Gnomad4 FIN exome AF: 0.394

Gnomad4 NFE exome AF: 0.314

Gnomad4 OTH exome AF: 0.325

GnomAD4 genome AF: 0.356 AC: 54077 AN: 151938 Hom.: 9870 Cov.: 32 AF XY: 0.364 AC XY: 27040 AN XY: 74270

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.407

Gnomad4 FIN AF: 0.389

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.373

Alfa AF: 0.350 Hom.: 4953

Bravo AF: 0.360

Asia WGS AF: 0.408 AC: 1418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0040
DANN	Benign	0.69

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: rs2930961; hg19: chr8-95443806;