NM_004112.4:c.488G>A

Variant names:

• chr17-7442673-G-A
• rs548703936
• NM_004112.4:c.488G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004112.4(FGF11):​c.488G>A​(p.Arg163His) variant causes a missense change. The variant allele was found at a frequency of 0.000372 in 1,614,102 control chromosomes in the GnomAD database, including 7 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R163L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00039 (7 hom.)
• Consequence: FGF11 NM_004112.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.50
• Publications: 1 publications found

Genes affected

FGF11 (HGNC:3667): (fibroblast growth factor 11) The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. The function of this gene has not yet been determined. The expression pattern of the mouse homolog implies a role in nervous system development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

ENSG00000272884 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012826413).
• BS2: High AC in GnomAd4 at 26 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004112.4. 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
	FGF11	NM_004112.4	MANE Select	c.488G>A	p.Arg163His	missense	Exon 4 of 5	NP_004103.1	Q92914
	FGF11	NM_001303460.2		c.311G>A	p.Arg104His	missense	Exon 4 of 5	NP_001290389.1	B7Z1C3
	FGF11	NR_130156.2		n.528G>A		non_coding_transcript_exon	Exon 4 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF11	ENST00000293829.9	TSL:1 MANE Select	c.488G>A	p.Arg163His	missense	Exon 4 of 5	ENSP00000293829.4	Q92914
	FGF11	ENST00000572907.5	TSL:1	c.116G>A	p.Arg39His	missense	Exon 3 of 4	ENSP00000465134.1	I3L4N4
	FGF11	ENST00000575235.5	TSL:1	c.116G>A	p.Arg39His	missense	Exon 4 of 5	ENSP00000459746.1	I3L4N4

Frequencies

GnomAD3 genomes AF: 0.000178 AC: 27 AN: 152098 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000712 AC: 179 AN: 251490 AF XY: 0.00100

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: 0.00

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000393 AC: 574 AN: 1461886 Hom.: 7 Cov.: 34 AF XY: 0.000560 AC XY: 407 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39700

South Asian (SAS) AF: 0.00633 AC: 546 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1112010

Other (OTH) AF: 0.000215 AC: 13 AN: 60396

GnomAD4 genome AF: 0.000171 AC: 26 AN: 152216 Hom.: 0 Cov.: 32 AF XY: 0.000282 AC XY: 21 AN XY: 74416

African (AFR) AF: 0.00 AC: 0 AN: 41528

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00539 AC: 26 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.000774 AC: 94

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.78	D
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.013	T
MetaSVM	Uncertain	0.087	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		6.5
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.51
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.42
MutPred		0.49		Loss of MoRF binding (P = 0.0278)
MVP		0.92
MPC		0.20
ClinPred		0.21	T
GERP RS		5.2
Varity_R		0.57
gMVP		0.40
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs548703936; hg19: chr17-7345992; COSMIC: COSV53440541; COSMIC: COSV53440541;