rs3853818

Variant names:

• chr17-7442983-T-C
• rs3853818
• NM_004112.4:c.608-93T>C

Variant summary

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

The NM_004112.4(FGF11):​c.608-93T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 1,172,598 control chromosomes in the GnomAD database, including 166,920 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 0.46 (17568 hom., cov: 31)
  • Exomes 𝑓: 0.52 (149352 hom.)
• Consequence: FGF11 NM_004112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.103

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF11	NM_004112.4	c.608-93T>C		intron_variant	Intron 4 of 4	ENST00000293829.9	NP_004103.1
FGF11	NM_001303460.2	c.431-93T>C		intron_variant	Intron 4 of 4		NP_001290389.1
FGF11	NR_130156.2	n.648-93T>C		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF11	ENST00000293829.9	c.608-93T>C		intron_variant	Intron 4 of 4	1	NM_004112.4	ENSP00000293829.4

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70173 AN: 151834 Hom.: 17571 Cov.: 31

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.0325

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.508

GnomAD4 exome AF: 0.523 AC: 533550 AN: 1020646 Hom.: 149352 Cov.: 13 AF XY: 0.520 AC XY: 270786 AN XY: 520334

Gnomad4 AFR exome AF: 0.343 AC: 8422 AN: 24554

Gnomad4 AMR exome AF: 0.293 AC: 11164 AN: 38080

Gnomad4 ASJ exome AF: 0.584 AC: 11805 AN: 20214

Gnomad4 EAS exome AF: 0.0384 AC: 1446 AN: 37618

Gnomad4 SAS exome AF: 0.385 AC: 27015 AN: 70162

Gnomad4 FIN exome AF: 0.457 AC: 22967 AN: 50252

Gnomad4 NFE exome AF: 0.582 AC: 424805 AN: 729512

Gnomad4 Remaining exome AF: 0.507 AC: 23058 AN: 45502

GnomAD4 genome AF: 0.462 AC: 70180 AN: 151952 Hom.: 17568 Cov.: 31 AF XY: 0.451 AC XY: 33489 AN XY: 74276

Gnomad4 AFR AF: 0.353 AC: 0.35318 AN: 0.35318

Gnomad4 AMR AF: 0.394 AC: 0.394354 AN: 0.394354

Gnomad4 ASJ AF: 0.581 AC: 0.580738 AN: 0.580738

Gnomad4 EAS AF: 0.0326 AC: 0.0326129 AN: 0.0326129

Gnomad4 SAS AF: 0.385 AC: 0.38543 AN: 0.38543

Gnomad4 FIN AF: 0.443 AC: 0.442581 AN: 0.442581

Gnomad4 NFE AF: 0.574 AC: 0.573671 AN: 0.573671

Gnomad4 OTH AF: 0.503 AC: 0.502838 AN: 0.502838

Alfa AF: 0.552 Hom.: 38739

Bravo AF: 0.454

Asia WGS AF: 0.196 AC: 683 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.5
DANN	Benign	0.58
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

Publications

LitVar

Other links and lift over

dbSNP: rs3853818; hg19: chr17-7346302; COSMIC: COSV53439221; COSMIC: COSV53439221;