Genetic Variant FAM227B:c.1012+46876A>G (chr15-49461335-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_152647.3(FAM227B):c.1012+46876A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,202 control chromosomes in the GnomAD database, including 5,774 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 0.25 ( 5774 hom., cov: 32)

Consequence

FAM227B
NM_152647.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.826

Publications

2 publications found

Variant links:

Genes affected

FAM227B (HGNC:26543): (family with sequence similarity 227 member B)

FAM227B links:

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]

FGF7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM227B	NM_152647.3 link	c.1012+46876A>G		intron_variant	Intron 11 of 15	ENST00000299338.11	NP_689860.2
FGF7	NM_002009.4 link	c.287-21816T>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 link	c.1012+46876A>G		intron_variant	Intron 11 of 15	2	NM_152647.3	ENSP00000299338.6
FGF7	ENST00000267843.9 link	c.287-21816T>C		intron_variant	Intron 2 of 3	1	NM_002009.4	ENSP00000267843.4

Frequencies

GnomAD3 genomes

AF:

0.254

AC:

38678

AN:

152084

Hom.:

5773

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0998

Gnomad AMI

AF:

0.444

Gnomad AMR

AF:

0.247

Gnomad ASJ

AF:

0.355

Gnomad EAS

AF:

0.182

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.284

Gnomad MID

AF:

0.239

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.273

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

GnomAD4 genome

AF:

0.254

AC:

38665

AN:

152202

Hom.:

5774

Cov.:

AF XY:

0.251

AC XY:

18670

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.0997

AC:

4142

AN:

41560

American (AMR)

AF:

0.246

AC:

3762

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.355

AC:

1230

AN:

3468

East Asian (EAS)

AF:

0.183

AC:

948

AN:

5180

South Asian (SAS)

AF:

0.200

AC:

964

AN:

4824

European-Finnish (FIN)

AF:

0.284

AC:

3012

AN:

10590

Middle Eastern (MID)

AF:

0.229

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.347

AC:

23568

AN:

67992

Other (OTH)

AF:

0.268

AC:

567

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1455

2910

4365

5820

7275

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

398

796

1194

1592

1990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.282

Hom.:

891

Bravo

AF:

0.244

Asia WGS

AF:

0.176

AC:

613

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.7

(source)

DANN

Benign

0.58

PhyloP100

-0.83

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over