rs2956724

Variant names:

• chr8-38434748-C-A
• rs2956724
• NM_023110.3:c.92-4800G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-38434748-C-A
• chr8-38434748-C-G

Variant summary

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

The NM_023110.3(FGFR1):​c.92-4800G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0802 in 159,242 control chromosomes in the GnomAD database, including 834 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 0.079 (796 hom., cov: 32)
  • Exomes 𝑓: 0.098 (38 hom.)
• Consequence: FGFR1 NM_023110.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.382
• Publications: 4 publications found

Genes affected

FGFR1 (HGNC:3688): (fibroblast growth factor receptor 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 consists 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. This particular family member binds both acidic and basic fibroblast growth factors and is involved in limb induction. Mutations in this gene have been associated with Pfeiffer syndrome, Jackson-Weiss syndrome, Antley-Bixler syndrome, osteoglophonic dysplasia, and autosomal dominant Kallmann syndrome 2. Chromosomal aberrations involving this gene are associated with stem cell myeloproliferative disorder and stem cell leukemia lymphoma syndrome. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

ENSG00000293142 (HGNC:):

RPS20P22 (HGNC:36379): (ribosomal protein S20 pseudogene 22)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023110.3. 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
	FGFR1	NM_023110.3	MANE Select	c.92-4800G>T		intron	N/A	NP_075598.2
	FGFR1	NM_001174067.2		c.191-4800G>T		intron	N/A	NP_001167538.1
	FGFR1	NM_001354367.2		c.92-4800G>T		intron	N/A	NP_001341296.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGFR1	ENST00000447712.7	TSL:1 MANE Select	c.92-4800G>T		intron	N/A	ENSP00000400162.2
	FGFR1	ENST00000425967.8	TSL:1	c.92-4800G>T		intron	N/A	ENSP00000393312.4
	FGFR1	ENST00000397091.9	TSL:1	c.92-4800G>T		intron	N/A	ENSP00000380280.5

Frequencies

GnomAD3 genomes AF: 0.0795 AC: 12088 AN: 152122 Hom.: 794 Cov.: 32

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0813

Gnomad ASJ AF: 0.0403

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0850

Gnomad OTH AF: 0.0621

GnomAD4 exome AF: 0.0975 AC: 683 AN: 7002 Hom.: 38 Cov.: 0 AF XY: 0.104 AC XY: 391 AN XY: 3754

African (AFR) AF: 0.0339 AC: 4 AN: 118

American (AMR) AF: 0.106 AC: 19 AN: 180

Ashkenazi Jewish (ASJ) AF: 0.00813 AC: 2 AN: 246

East Asian (EAS) AF: 0.276 AC: 74 AN: 268

South Asian (SAS) AF: 0.152 AC: 93 AN: 610

European-Finnish (FIN) AF: 0.147 AC: 54 AN: 368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 36

European-Non Finnish (NFE) AF: 0.0852 AC: 403 AN: 4732

Other (OTH) AF: 0.0766 AC: 34 AN: 444

GnomAD4 genome AF: 0.0794 AC: 12093 AN: 152240 Hom.: 796 Cov.: 32 AF XY: 0.0870 AC XY: 6479 AN XY: 74434

African (AFR) AF: 0.0146 AC: 607 AN: 41556

American (AMR) AF: 0.0812 AC: 1242 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0403 AC: 140 AN: 3472

East Asian (EAS) AF: 0.304 AC: 1573 AN: 5180

South Asian (SAS) AF: 0.173 AC: 836 AN: 4820

European-Finnish (FIN) AF: 0.164 AC: 1739 AN: 10590

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0850 AC: 5779 AN: 68012

Other (OTH) AF: 0.0657 AC: 139 AN: 2116

Alfa AF: 0.0812 Hom.: 92

Bravo AF: 0.0666

Asia WGS AF: 0.209 AC: 725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.1
DANN	Benign	0.58
PhyloP100		-0.38
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: rs2956724; hg19: chr8-38292266;