rs12494994

Variant names:

• chr3-100103692-C-T
• rs12494994
• NM_001387850.1:c.-11+10361G>A

Variant summary

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

The NM_001387850.1(FILIP1L):​c.-11+10361G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,110 control chromosomes in the GnomAD database, including 2,396 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 0.18 (2396 hom., cov: 32)
• Consequence: FILIP1L NM_001387850.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56
• Publications: 6 publications found

Genes affected

FILIP1L (HGNC:24589): (filamin A interacting protein 1 like) Predicted to be located in cytoplasm; membrane; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

CMSS1 (HGNC:28666): (cms1 ribosomal small subunit homolog) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FILIP1L	NM_001387850.1	c.-11+10361G>A		intron_variant	Intron 1 of 5	ENST00000477258.2	NP_001374779.1
CMSS1	NM_032359.4	c.65-43281C>T		intron_variant	Intron 1 of 9	ENST00000421999.8	NP_115735.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FILIP1L	ENST00000477258.2	c.-11+10361G>A		intron_variant	Intron 1 of 5	2	NM_001387850.1	ENSP00000417617.2
CMSS1	ENST00000421999.8	c.65-43281C>T		intron_variant	Intron 1 of 9	1	NM_032359.4	ENSP00000410396.2

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26604 AN: 151990 Hom.: 2390 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.0865

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.175 AC: 26643 AN: 152110 Hom.: 2396 Cov.: 32 AF XY: 0.175 AC XY: 13048 AN XY: 74378

African (AFR) AF: 0.186 AC: 7720 AN: 41486

American (AMR) AF: 0.176 AC: 2684 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0865 AC: 300 AN: 3468

East Asian (EAS) AF: 0.119 AC: 614 AN: 5180

South Asian (SAS) AF: 0.200 AC: 963 AN: 4820

European-Finnish (FIN) AF: 0.174 AC: 1841 AN: 10590

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11987 AN: 67970

Other (OTH) AF: 0.176 AC: 370 AN: 2108

Alfa AF: 0.172 Hom.: 5560

Bravo AF: 0.174

Asia WGS AF: 0.174 AC: 605 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.7
DANN	Benign	0.32
PhyloP100		1.6
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: rs12494994; hg19: chr3-99822536;