chr8-94431578-T-C

Variant names:

• chr8-94431578-T-C
• rs2930961
• NM_001256141.2:c.*553A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FSBP	NM_001256141.2	c.*553A>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000481490.3	NP_001243070.1
RAD54B	NM_012415.3	c.305-20263A>G		intron_variant	Intron 3 of 14	ENST00000336148.10	NP_036547.1
RAD54B	NM_001205262.3	c.*1029A>G		3_prime_UTR_variant	Exon 4 of 4		NP_001192191.1
RAD54B	NM_001205263.2	c.-249+4917A>G		intron_variant	Intron 1 of 12		NP_001192192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSBP	ENST00000481490.3	c.*553A>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_001256141.2	ENSP00000420405.2
RAD54B	ENST00000336148.10	c.305-20263A>G		intron_variant	Intron 3 of 14	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

African (AFR) AF: 0.345 AC: 5019 AN: 14540

American (AMR) AF: 0.523 AC: 483 AN: 924

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1624 AN: 4852

East Asian (EAS) AF: 0.468 AC: 1572 AN: 3360

South Asian (SAS) AF: 0.399 AC: 6131 AN: 15354

European-Finnish (FIN) AF: 0.394 AC: 97 AN: 246

Middle Eastern (MID) AF: 0.353 AC: 537 AN: 1520

European-Non Finnish (NFE) AF: 0.314 AC: 223644 AN: 713140

Other (OTH) AF: 0.325 AC: 8277 AN: 25486

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

African (AFR) AF: 0.333 AC: 13816 AN: 41438

American (AMR) AF: 0.470 AC: 7165 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1137 AN: 3472

East Asian (EAS) AF: 0.466 AC: 2408 AN: 5168

South Asian (SAS) AF: 0.407 AC: 1962 AN: 4816

European-Finnish (FIN) AF: 0.389 AC: 4095 AN: 10536

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22341 AN: 67940

Other (OTH) AF: 0.373 AC: 787 AN: 2112

Alfa AF: 0.347 Hom.: 5418

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
PhyloP100		-3.6
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: rs2930961; hg19: chr8-95443806;