rs4647940

Variant names:

• chr4-1026603-C-G
• rs4647940
• NM_001004356.3:c.*1256C>G

Your query was ambiguous. Multiple possible variants found:

• chr4-1026603-C-G
• chr4-1026603-C-T

Variant summary

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

The NM_001004356.3(FGFRL1):​c.*1256C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 259,074 control chromosomes in the GnomAD database, including 2,637 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 0.13 (1293 hom., cov: 34)
  • Exomes 𝑓: 0.15 (1344 hom.)
• Consequence: FGFRL1 NM_001004356.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.332
• Publications: 12 publications found

Genes affected

FGFRL1 (HGNC:3693): (fibroblast growth factor receptor like 1) The protein encoded by this gene is a member of the fibroblast growth factor receptor (FGFR) family, where amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein would consist of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. A marked difference between this gene product and the other family members is its lack of a cytoplasmic tyrosine kinase domain. The result is a transmembrane receptor that could interact with other family members and potentially inhibit signaling. Multiple alternatively spliced transcript variants encoding the same isoform have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGFRL1	NM_001004356.3	c.*1256C>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000510644.6	NP_001004356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGFRL1	ENST00000510644.6	c.*1256C>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_001004356.3	ENSP00000425025.1
FGFRL1	ENST00000264748.6	c.*1256C>G		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000264748.6
FGFRL1	ENST00000398484.6	c.*1256C>G		3_prime_UTR_variant	Exon 8 of 8	5		ENSP00000381498.2

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19092 AN: 152138 Hom.: 1294 Cov.: 34

Gnomad AFR AF: 0.0785

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.0985

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.141

GnomAD4 exome AF: 0.150 AC: 16055 AN: 106818 Hom.: 1344 Cov.: 0 AF XY: 0.156 AC XY: 9165 AN XY: 58730

African (AFR) AF: 0.0775 AC: 147 AN: 1896

American (AMR) AF: 0.0739 AC: 212 AN: 2870

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 345 AN: 2698

East Asian (EAS) AF: 0.149 AC: 339 AN: 2274

South Asian (SAS) AF: 0.201 AC: 4153 AN: 20668

European-Finnish (FIN) AF: 0.148 AC: 884 AN: 5982

Middle Eastern (MID) AF: 0.184 AC: 72 AN: 392

European-Non Finnish (NFE) AF: 0.142 AC: 9157 AN: 64594

Other (OTH) AF: 0.137 AC: 746 AN: 5444

GnomAD4 genome AF: 0.125 AC: 19086 AN: 152256 Hom.: 1293 Cov.: 34 AF XY: 0.126 AC XY: 9373 AN XY: 74448

African (AFR) AF: 0.0784 AC: 3257 AN: 41548

American (AMR) AF: 0.0982 AC: 1503 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 461 AN: 3472

East Asian (EAS) AF: 0.152 AC: 789 AN: 5176

South Asian (SAS) AF: 0.208 AC: 1005 AN: 4822

European-Finnish (FIN) AF: 0.144 AC: 1523 AN: 10608

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10071 AN: 68008

Other (OTH) AF: 0.139 AC: 293 AN: 2112

Alfa AF: 0.0560 Hom.: 64

Bravo AF: 0.120

Asia WGS AF: 0.161 AC: 565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.1
DANN	Benign	0.71
PhyloP100		0.33
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: rs4647940; hg19: chr4-1020391;