chr15-49468228-G-T

Variant names:

• chr15-49468228-G-T
• rs2413959
• NM_152647.3:c.1012+39983C>A

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+39983C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 151,934 control chromosomes in the GnomAD database, including 8,720 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 0.32 (8720 hom., cov: 32)
• Consequence: FAM227B NM_152647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308
• Publications: 1 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM227B	NM_152647.3	c.1012+39983C>A		intron_variant	Intron 11 of 15	ENST00000299338.11	NP_689860.2
FGF7	NM_002009.4	c.287-14923G>T		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+39983C>A		intron_variant	Intron 11 of 15	2	NM_152647.3	ENSP00000299338.6
FGF7	ENST00000267843.9	c.287-14923G>T		intron_variant	Intron 2 of 3	1	NM_002009.4	ENSP00000267843.4

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49231 AN: 151816 Hom.: 8708 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.324 AC: 49289 AN: 151934 Hom.: 8720 Cov.: 32 AF XY: 0.323 AC XY: 23966 AN XY: 74256

African (AFR) AF: 0.452 AC: 18743 AN: 41452

American (AMR) AF: 0.376 AC: 5737 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 752 AN: 3470

East Asian (EAS) AF: 0.381 AC: 1974 AN: 5178

South Asian (SAS) AF: 0.280 AC: 1351 AN: 4818

European-Finnish (FIN) AF: 0.244 AC: 2567 AN: 10524

Middle Eastern (MID) AF: 0.360 AC: 105 AN: 292

European-Non Finnish (NFE) AF: 0.253 AC: 17218 AN: 67942

Other (OTH) AF: 0.322 AC: 678 AN: 2108

Alfa AF: 0.288 Hom.: 843

Bravo AF: 0.343

Asia WGS AF: 0.326 AC: 1132 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.9
DANN	Benign	0.43
PhyloP100		-0.31
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: rs2413959; hg19: chr15-49760425;