rs370619260

Variant names:

• chr11-65884433-C-T
• rs370619260
• NM_004214.5:c.963G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-65884433-C-T
• chr11-65884433-C-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6 BP7

The NM_004214.5(FIBP):​c.963G>A​(p.Leu321Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000153 in 1,614,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: FIBP NM_004214.5 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.860
• Publications: 0 publications found

Genes affected

FIBP (HGNC:3705): (FGF1 intracellular binding protein) Acidic fibroblast growth factor is mitogenic for a variety of different cell types and acts by stimulating mitogenesis or inducing morphological changes and differentiation. The FIBP protein is an intracellular protein that binds selectively to acidic fibroblast growth factor (aFGF). It is postulated that FIBP may be involved in the mitogenic action of aFGF. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

FIBP Gene-Disease associations (from GenCC):

• tall stature-intellectual disability-renal anomalies syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.081952095).
• BP6: Variant 11-65884433-C-T is Benign according to our data. Variant chr11-65884433-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3048041.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.86 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004214.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FIBP	NM_004214.5	MANE Select	c.963G>A	p.Leu321Leu	synonymous	Exon 9 of 10	NP_004205.2
	FIBP	NM_198897.2		c.984G>A	p.Leu328Leu	synonymous	Exon 9 of 10	NP_942600.1	O43427-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FIBP	ENST00000357519.9	TSL:1 MANE Select	c.963G>A	p.Leu321Leu	synonymous	Exon 9 of 10	ENSP00000350124.5	O43427-2
	FIBP	ENST00000338369.6	TSL:1	c.984G>A	p.Leu328Leu	synonymous	Exon 9 of 10	ENSP00000344572.2	O43427-1
	FIBP	ENST00000533045.5	TSL:5	c.940G>A	p.Glu314Lys	missense	Exon 9 of 10	ENSP00000434043.1	E9PSD3

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152168 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000478 AC: 12 AN: 251210 AF XY: 0.0000515

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000969

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000153 AC: 224 AN: 1461868 Hom.: 0 Cov.: 34 AF XY: 0.000173 AC XY: 126 AN XY: 727240

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000195 AC: 217 AN: 1112006

Other (OTH) AF: 0.0000993 AC: 6 AN: 60396

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152168 Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7 AN XY: 74328

African (AFR) AF: 0.0000483 AC: 2 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000249 Hom.: 0

Bravo AF: 0.000110

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000659 AC: 8

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	FIBP-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	9.2
DANN	Benign	0.96
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.41
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.86
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.015
Sift	Pathogenic	0.0	D
Polyphen		0.0020	B
Vest4		0.15
MVP		0.34
ClinPred		0.066	T
GERP RS		1.8
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs370619260; hg19: chr11-65651904;