dbSNP rs143032930: FETUB:c.336+8C>T (chr3-186641148-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_014375.3(FETUB):c.336+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0015 in 1,571,710 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0077 ( 13 hom., cov: 32)

Exomes 𝑓: 0.00083 ( 24 hom. )

Consequence

FETUB
NM_014375.3 splice_region, intron

Scores

Splicing: ADA: 0.0004438

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.341

Publications

0 publications found

Variant links:

Genes affected

FETUB (HGNC:3658): (fetuin B) The protein encoded by this gene is a member of the fetuin family, part of the cystatin superfamily of cysteine protease inhibitors. Fetuins have been implicated in several diverse functions, including osteogenesis and bone resorption, regulation of the insulin and hepatocyte growth factor receptors, and response to systemic inflammation. This protein may be secreted by cells. [provided by RefSeq, Jul 2008]

FETUB links:

HRG-AS1 (HGNC:55915): (HRG and FETUB antisense RNA 1)

HRG-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 3-186641148-C-T is Benign according to our data. Variant chr3-186641148-C-T is described in ClinVar as Benign. ClinVar VariationId is 775933.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00771 (1173/152236) while in subpopulation AFR AF = 0.0269 (1117/41546). AF 95% confidence interval is 0.0256. There are 13 homozygotes in GnomAd4. There are 554 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014375.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FETUB	NM_014375.3	MANE Select	c.336+8C>T	splice_region intron	N/A	NP_055190.2	Q9UGM5-1
FETUB	NM_001375587.2		c.336+8C>T	splice_region intron	N/A	NP_001362516.1	Q9UGM5-1
FETUB	NM_001308077.4		c.225+463C>T	intron	N/A	NP_001295006.1	Q9UGM5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FETUB	ENST00000265029.8	TSL:1 MANE Select	c.336+8C>T	splice_region intron	N/A	ENSP00000265029.3	Q9UGM5-1
FETUB	ENST00000450521.5	TSL:1	c.336+8C>T	splice_region intron	N/A	ENSP00000404288.1	Q9UGM5-1
FETUB	ENST00000382136.3	TSL:1	c.225+463C>T	intron	N/A	ENSP00000371571.3	Q9UGM5-2

Frequencies

GnomAD3 genomes

AF:

0.00765

AC:

1163

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0267

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00190

AC:

459

AN:

242026

AF XY:

0.00133

show subpopulations

Gnomad AFR exome

AF:

0.0268

Gnomad AMR exome

AF:

0.000890

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000168

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000184

Gnomad OTH exome

AF:

0.00151

GnomAD4 exome

AF:

0.000834

AC:

1184

AN:

1419474

Hom.:

Cov.:

AF XY:

0.000688

AC XY:

487

AN XY:

708356

show subpopulations

African (AFR)

AF:

0.0313

AC:

1019

AN:

32586

American (AMR)

AF:

0.00111

AC:

AN:

44124

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25762

East Asian (EAS)

AF:

0.000101

AC:

AN:

39430

South Asian (SAS)

AF:

0.0000828

AC:

AN:

84556

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53136

Middle Eastern (MID)

AF:

0.000700

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.0000112

AC:

AN:

1075266

Other (OTH)

AF:

0.00151

AC:

AN:

58898

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

119

178

238

297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00771

AC:

1173

AN:

152236

Hom.:

Cov.:

AF XY:

0.00744

AC XY:

554

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0269

AC:

1117

AN:

41546

American (AMR)

AF:

0.00288

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68004

Other (OTH)

AF:

0.00331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

111

166

222

277

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<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:

0.00694

Hom.:

Bravo

AF:

0.00902

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

9.7

(source)

DANN

Benign

0.65

PhyloP100

0.34

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00044

dbscSNV1_RF

Benign

0.066

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over