rs2121875

Variant names:

• chr5-44365443-C-A
• rs2121875
• NM_004465.2:c.325+22915G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-44365443-C-A
• chr5-44365443-C-G
• chr5-44365443-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004465.2(FGF10):​c.325+22915G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 151,194 control chromosomes in the GnomAD database, including 23,722 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.54 (23722 hom., cov: 30)
• Consequence: FGF10 NM_004465.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0450
• Publications: 67 publications found

Genes affected

FGF10 (HGNC:3666): (fibroblast growth factor 10) 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. This protein exhibits mitogenic activity for keratinizing epidermal cells, but essentially no activity for fibroblasts, which is similar to the biological activity of FGF7. Studies of the mouse homolog of suggested that this gene is required for embryonic epidermal morphogenesis including brain development, lung morphogenesis, and initiation of lim bud formation. This gene is also implicated to be a primary factor in the process of wound healing. [provided by RefSeq, Jul 2008]

FGF10 Gene-Disease associations (from GenCC):

• lacrimoauriculodentodigital syndrome 3

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• aplasia of lacrimal and salivary glands

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• LADD syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• congenital heart defects, multiple types

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• craniosynostosis

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 5-44365443-C-A is Benign according to our data. Variant chr5-44365443-C-A is described in ClinVar as Benign. ClinVar VariationId is 1663361.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004465.2. 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
	FGF10	NM_004465.2	MANE Select	c.325+22915G>T		intron	N/A	NP_004456.1	O15520

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF10	ENST00000264664.5	TSL:1 MANE Select	c.325+22915G>T		intron	N/A	ENSP00000264664.4	O15520
	FGF10	ENST00000912799.1		c.325+22915G>T		intron	N/A	ENSP00000582858.1

Frequencies

GnomAD3 genomes AF: 0.535 AC: 80899 AN: 151086 Hom.: 23723 Cov.: 30

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.561

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.535 AC: 80909 AN: 151194 Hom.: 23722 Cov.: 30 AF XY: 0.537 AC XY: 39664 AN XY: 73828

African (AFR) AF: 0.283 AC: 11659 AN: 41184

American (AMR) AF: 0.475 AC: 7195 AN: 15140

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 2299 AN: 3460

East Asian (EAS) AF: 0.495 AC: 2518 AN: 5088

South Asian (SAS) AF: 0.609 AC: 2924 AN: 4800

European-Finnish (FIN) AF: 0.664 AC: 6949 AN: 10464

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.670 AC: 45420 AN: 67748

Other (OTH) AF: 0.556 AC: 1170 AN: 2104

Alfa AF: 0.629 Hom.: 114195

Bravo AF: 0.507

Asia WGS AF: 0.467 AC: 1623 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Benign	0.62
PhyloP100		0.045
Mutation Taster		=98/2	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: rs2121875; hg19: chr5-44365545;