rs17478694

Variant names:

• chr15-49446345-C-G
• rs17478694
• NM_152647.3:c.1012+61866G>C

Variant summary

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

The NM_152647.3(FAM227B):​c.1012+61866G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 151,402 control chromosomes in the GnomAD database, including 6,842 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 0.27 (6842 hom., cov: 32)
• Consequence: FAM227B NM_152647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.144
• Publications: 2 publications found

Genes affected

FAM227B (HGNC:26543): (family with sequence similarity 227 member B)

FGF7 (HGNC:3685): (fibroblast growth factor 7) 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 is a potent epithelial cell-specific growth factor, whose mitogenic activity is predominantly exhibited in keratinocytes but not in fibroblasts and endothelial cells. Studies of mouse and rat homologs of this gene implicated roles in morphogenesis of epithelium, reepithelialization of wounds, hair development and early lung organogenesis. [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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM227B	NM_152647.3	c.1012+61866G>C		intron_variant	Intron 11 of 15	ENST00000299338.11	NP_689860.2
FGF7	NM_002009.4	c.286+21762C>G		intron_variant	Intron 2 of 3	ENST00000267843.9	NP_002000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM227B	ENST00000299338.11	c.1012+61866G>C		intron_variant	Intron 11 of 15	2	NM_152647.3	ENSP00000299338.6
FGF7	ENST00000267843.9	c.286+21762C>G		intron_variant	Intron 2 of 3	1	NM_002009.4	ENSP00000267843.4

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41203 AN: 151284 Hom.: 6841 Cov.: 32

Gnomad AFR AF: 0.0888

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.272 AC: 41186 AN: 151402 Hom.: 6842 Cov.: 32 AF XY: 0.270 AC XY: 20008 AN XY: 73970

African (AFR) AF: 0.0886 AC: 3672 AN: 41446

American (AMR) AF: 0.265 AC: 4018 AN: 15154

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1479 AN: 3456

East Asian (EAS) AF: 0.186 AC: 955 AN: 5138

South Asian (SAS) AF: 0.210 AC: 1010 AN: 4818

European-Finnish (FIN) AF: 0.338 AC: 3569 AN: 10562

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.375 AC: 25355 AN: 67534

Other (OTH) AF: 0.280 AC: 586 AN: 2090

Alfa AF: 0.318 Hom.: 1075

Bravo AF: 0.259

Asia WGS AF: 0.179 AC: 621 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.5
DANN	Benign	0.66
PhyloP100		0.14
Mutation Taster		=99/1	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: rs17478694; hg19: chr15-49738542;