rs17478785

Variant names:

• chr15-49448107-A-C
• rs17478785
• NM_152647.3:c.1012+60104T>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+60104T>G 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 151,538 control chromosomes in the GnomAD database, including 6,853 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 (6853 hom., cov: 31)
• Consequence: FAM227B NM_152647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.929
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152647.3. 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
	FAM227B	NM_152647.3	MANE Select	c.1012+60104T>G		intron	N/A	NP_689860.2	Q96M60-1
	FGF7	NM_002009.4	MANE Select	c.286+23524A>C		intron	N/A	NP_002000.1	P21781-1
	FAM227B	NM_001330293.2		c.911-25393T>G		intron	N/A	NP_001317222.1	Q96M60-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM227B	ENST00000299338.11	TSL:2 MANE Select	c.1012+60104T>G		intron	N/A	ENSP00000299338.6	Q96M60-1
	FGF7	ENST00000267843.9	TSL:1 MANE Select	c.286+23524A>C		intron	N/A	ENSP00000267843.4	P21781-1
	FAM227B	ENST00000561064.5	TSL:1	c.911-25393T>G		intron	N/A	ENSP00000453028.1	Q96M60-2

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41300 AN: 151420 Hom.: 6852 Cov.: 31

Gnomad AFR AF: 0.0888

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.272 AC: 41283 AN: 151538 Hom.: 6853 Cov.: 31 AF XY: 0.271 AC XY: 20051 AN XY: 74036

African (AFR) AF: 0.0887 AC: 3678 AN: 41488

American (AMR) AF: 0.266 AC: 4029 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 1487 AN: 3460

East Asian (EAS) AF: 0.185 AC: 950 AN: 5134

South Asian (SAS) AF: 0.210 AC: 1013 AN: 4818

European-Finnish (FIN) AF: 0.336 AC: 3545 AN: 10546

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.376 AC: 25439 AN: 67624

Other (OTH) AF: 0.283 AC: 594 AN: 2098

Alfa AF: 0.318 Hom.: 1075

Bravo AF: 0.260

Asia WGS AF: 0.178 AC: 619 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.19
DANN	Benign	0.69
PhyloP100		-0.93
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: rs17478785; hg19: chr15-49740304;