rs748463485

Variant names:

• chr12-132490740-C-G
• rs748463485
• NM_001367871.1:c.170C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-132490740-C-G
• chr12-132490740-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001367871.1(FBRSL1):​c.170C>G​(p.Ala57Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000232 in 862,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A57T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: FBRSL1 NM_001367871.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94

Genes affected

FBRSL1 (HGNC:29308): (fibrosin like 1) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23464075).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBRSL1	NM_001367871.1	c.170C>G	p.Ala57Gly	missense_variant	Exon 1 of 19	ENST00000680143.1	NP_001354800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBRSL1	ENST00000680143.1	c.170C>G	p.Ala57Gly	missense_variant	Exon 1 of 19		NM_001367871.1	ENSP00000505341.1
FBRSL1	ENST00000434748.2	c.170C>G	p.Ala57Gly	missense_variant	Exon 1 of 17	1		ENSP00000396160.2
FBRSL1	ENST00000650108.1	c.170C>G	p.Ala57Gly	missense_variant	Exon 1 of 20			ENSP00000496901.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000232 AC: 2 AN: 862488 Hom.: 0 Cov.: 28 AF XY: 0.00000499 AC XY: 2 AN XY: 400806

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000256

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.00083	T;.
Eigen	Benign	-0.0059
Eigen_PC	Benign	0.030
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.31	T;T
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.33	N;.
REVEL	Benign	0.098
Sift	Benign	0.51	T;.
Sift4G	Benign	0.21	T;.
Polyphen		0.99	D;.
Vest4		0.068
MutPred		0.21		Gain of relative solvent accessibility (P = 0.0023);Gain of relative solvent accessibility (P = 0.0023);
MVP		0.040
ClinPred		0.59	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.091
gMVP		0.099

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: rs748463485; hg19: chr12-133067326;