15-49457351-T-C

Variant names:

• chr15-49457351-T-C
• rs11634375
• NM_152647.3:c.1012+50860A>G

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+50860A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 151,722 control chromosomes in the GnomAD database, including 16,572 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 0.44 (16572 hom., cov: 32)
• Consequence: FAM227B NM_152647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM227B	NM_152647.3	c.1012+50860A>G		intron_variant	Intron 11 of 15	ENST00000299338.11	NP_689860.2
FGF7	NM_002009.4	c.287-25800T>C		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+50860A>G		intron_variant	Intron 11 of 15	2	NM_152647.3	ENSP00000299338.6
FGF7	ENST00000267843.9	c.287-25800T>C		intron_variant	Intron 2 of 3	1	NM_002009.4	ENSP00000267843.4

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67144 AN: 151602 Hom.: 16571 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.443 AC: 67150 AN: 151722 Hom.: 16572 Cov.: 32 AF XY: 0.445 AC XY: 32988 AN XY: 74140

African (AFR) AF: 0.214 AC: 8850 AN: 41446

American (AMR) AF: 0.504 AC: 7677 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1833 AN: 3468

East Asian (EAS) AF: 0.291 AC: 1503 AN: 5168

South Asian (SAS) AF: 0.563 AC: 2720 AN: 4828

European-Finnish (FIN) AF: 0.523 AC: 5498 AN: 10504

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.554 AC: 37556 AN: 67758

Other (OTH) AF: 0.462 AC: 971 AN: 2102

Alfa AF: 0.523 Hom.: 34376

Bravo AF: 0.429

Asia WGS AF: 0.414 AC: 1440 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.8
DANN	Benign	0.46
PhyloP100		0.17
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: rs11634375; hg19: chr15-49749548;