chr15-49468349-A-G

Variant names:

• chr15-49468349-A-G
• rs2413958
• NM_152647.3:c.1012+39862T>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+39862T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 151,964 control chromosomes in the GnomAD database, including 36,429 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 0.69 (36429 hom., cov: 32)
• Consequence: FAM227B NM_152647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• Publications: 4 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM227B	NM_152647.3	c.1012+39862T>C		intron_variant	Intron 11 of 15	ENST00000299338.11	NP_689860.2
FGF7	NM_002009.4	c.287-14802A>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+39862T>C		intron_variant	Intron 11 of 15	2	NM_152647.3	ENSP00000299338.6
FGF7	ENST00000267843.9	c.287-14802A>G		intron_variant	Intron 2 of 3	1	NM_002009.4	ENSP00000267843.4

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104671 AN: 151846 Hom.: 36406 Cov.: 32

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.724

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.697

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

GnomAD4 genome AF: 0.689 AC: 104738 AN: 151964 Hom.: 36429 Cov.: 32 AF XY: 0.689 AC XY: 51171 AN XY: 74272

African (AFR) AF: 0.594 AC: 24585 AN: 41420

American (AMR) AF: 0.767 AC: 11705 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.724 AC: 2514 AN: 3470

East Asian (EAS) AF: 0.925 AC: 4795 AN: 5184

South Asian (SAS) AF: 0.681 AC: 3279 AN: 4816

European-Finnish (FIN) AF: 0.661 AC: 6987 AN: 10566

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.714 AC: 48497 AN: 67934

Other (OTH) AF: 0.693 AC: 1466 AN: 2114

Alfa AF: 0.611 Hom.: 2511

Bravo AF: 0.696

Asia WGS AF: 0.747 AC: 2600 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.71
PhyloP100		1.5
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: rs2413958; hg19: chr15-49760546;