chr17-7442647-C-T

Variant names:

• chr17-7442647-C-T
• rs4151130
• NM_004112.4:c.462C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_004112.4(FGF11):​c.462C>T​(p.Tyr154Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00774 in 1,614,198 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0055 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0080 (65 hom.)
• Consequence: FGF11 NM_004112.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.233
• Publications: 3 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 -12 ACMG points.

• BP6: Variant 17-7442647-C-T is Benign according to our data. Variant chr17-7442647-C-T is described in ClinVar as Benign. ClinVar VariationId is 771204.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 837 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.462C>T	p.Tyr154Tyr	synonymous	Exon 4 of 5	NP_004103.1	Q92914
	FGF11	NM_001303460.2		c.285C>T	p.Tyr95Tyr	synonymous	Exon 4 of 5	NP_001290389.1	B7Z1C3
	FGF11	NR_130156.2		n.502C>T		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.462C>T	p.Tyr154Tyr	synonymous	Exon 4 of 5	ENSP00000293829.4	Q92914
	FGF11	ENST00000572907.5	TSL:1	c.90C>T	p.Tyr30Tyr	synonymous	Exon 3 of 4	ENSP00000465134.1	I3L4N4
	FGF11	ENST00000575235.5	TSL:1	c.90C>T	p.Tyr30Tyr	synonymous	Exon 4 of 5	ENSP00000459746.1	I3L4N4

Frequencies

GnomAD3 genomes AF: 0.00551 AC: 838 AN: 152204 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.00458

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00766

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00901

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00606 AC: 1525 AN: 251494 AF XY: 0.00648

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.00341

Gnomad ASJ exome AF: 0.00377

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00203

Gnomad NFE exome AF: 0.00943

Gnomad OTH exome AF: 0.00537

GnomAD4 exome AF: 0.00797 AC: 11650 AN: 1461876 Hom.: 65 Cov.: 34 AF XY: 0.00791 AC XY: 5751 AN XY: 727242

African (AFR) AF: 0.00122 AC: 41 AN: 33480

American (AMR) AF: 0.00331 AC: 148 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00337 AC: 88 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00715 AC: 617 AN: 86252

European-Finnish (FIN) AF: 0.00204 AC: 109 AN: 53416

Middle Eastern (MID) AF: 0.00954 AC: 55 AN: 5768

European-Non Finnish (NFE) AF: 0.00914 AC: 10161 AN: 1112004

Other (OTH) AF: 0.00712 AC: 430 AN: 60396

GnomAD4 genome AF: 0.00549 AC: 837 AN: 152322 Hom.: 10 Cov.: 32 AF XY: 0.00513 AC XY: 382 AN XY: 74480

African (AFR) AF: 0.00115 AC: 48 AN: 41564

American (AMR) AF: 0.00458 AC: 70 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00766 AC: 37 AN: 4828

European-Finnish (FIN) AF: 0.00207 AC: 22 AN: 10622

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00901 AC: 613 AN: 68030

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.00695 Hom.: 4

Bravo AF: 0.00511

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0110

EpiControl AF: 0.0107

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	15
DANN	Benign	0.90
PhyloP100		-0.23
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.26		Position offset: 31

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4151130; hg19: chr17-7345966; COSMIC: COSV53440308; COSMIC: COSV53440308;