15-49441549-C-T

Variant names:

• chr15-49441549-C-T
• rs7168316
• NM_152647.3:c.1012+66662G>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+66662G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 151,384 control chromosomes in the GnomAD database, including 3,244 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 0.20 (3244 hom., cov: 31)
• Consequence: FAM227B NM_152647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156
• Publications: 11 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.316 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+66662G>A		intron	N/A	NP_689860.2	Q96M60-1
	FGF7	NM_002009.4	MANE Select	c.286+16966C>T		intron	N/A	NP_002000.1	P21781-1
	FAM227B	NM_001330293.2		c.911-18835G>A		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+66662G>A		intron	N/A	ENSP00000299338.6	Q96M60-1
	FGF7	ENST00000267843.9	TSL:1 MANE Select	c.286+16966C>T		intron	N/A	ENSP00000267843.4	P21781-1
	FAM227B	ENST00000561064.5	TSL:1	c.911-18835G>A		intron	N/A	ENSP00000453028.1	Q96M60-2

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30140 AN: 151266 Hom.: 3243 Cov.: 31

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.0845

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.199 AC: 30153 AN: 151384 Hom.: 3244 Cov.: 31 AF XY: 0.204 AC XY: 15055 AN XY: 73952

African (AFR) AF: 0.125 AC: 5191 AN: 41378

American (AMR) AF: 0.190 AC: 2889 AN: 15172

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 797 AN: 3452

East Asian (EAS) AF: 0.0849 AC: 432 AN: 5090

South Asian (SAS) AF: 0.330 AC: 1583 AN: 4804

European-Finnish (FIN) AF: 0.273 AC: 2877 AN: 10540

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15737 AN: 67646

Other (OTH) AF: 0.216 AC: 453 AN: 2098

Alfa AF: 0.224 Hom.: 6751

Bravo AF: 0.185

Asia WGS AF: 0.208 AC: 722 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.67
DANN	Benign	0.22
PhyloP100		-0.16
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: rs7168316; hg19: chr15-49733746;