chr12-132512822-T-C

Variant names:

• chr12-132512822-T-C
• rs2323991
• NM_001367871.1:c.489+4472T>C

Variant summary

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

The NM_001367871.1(FBRSL1):​c.489+4472T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.889 in 152,236 control chromosomes in the GnomAD database, including 61,279 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 0.89 (61279 hom., cov: 34)
• Consequence: FBRSL1 NM_001367871.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 1 publications found

Genes affected

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

FBRSL1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• syndromic complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Broad Center for Mendelian Genomics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBRSL1	NM_001367871.1	c.489+4472T>C		intron_variant	Intron 2 of 18	ENST00000680143.1	NP_001354800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBRSL1	ENST00000680143.1	c.489+4472T>C		intron_variant	Intron 2 of 18		NM_001367871.1	ENSP00000505341.1
FBRSL1	ENST00000434748.2	c.489+4472T>C		intron_variant	Intron 2 of 16	1		ENSP00000396160.2
FBRSL1	ENST00000650108.1	c.489+4472T>C		intron_variant	Intron 2 of 19			ENSP00000496901.1

Frequencies

GnomAD3 genomes AF: 0.889 AC: 135258 AN: 152118 Hom.: 61249 Cov.: 34

Gnomad AFR AF: 0.750

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.849

Gnomad ASJ AF: 0.983

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.955

Gnomad FIN AF: 0.941

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.988

Gnomad OTH AF: 0.912

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

GnomAD4 genome AF: 0.889 AC: 135341 AN: 152236 Hom.: 61279 Cov.: 34 AF XY: 0.885 AC XY: 65882 AN XY: 74430

African (AFR) AF: 0.750 AC: 31114 AN: 41506

American (AMR) AF: 0.849 AC: 12987 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.983 AC: 3412 AN: 3472

East Asian (EAS) AF: 0.563 AC: 2912 AN: 5170

South Asian (SAS) AF: 0.955 AC: 4615 AN: 4830

European-Finnish (FIN) AF: 0.941 AC: 9989 AN: 10618

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.988 AC: 67183 AN: 68022

Other (OTH) AF: 0.912 AC: 1928 AN: 2114

Alfa AF: 0.934 Hom.: 8317

Bravo AF: 0.874

Asia WGS AF: 0.815 AC: 2834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.32
DANN	Benign	0.50
PhyloP100		-1.4
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
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: rs2323991; hg19: chr12-133089408;