Genetic Variant AFM:c.1192-87T>C (chr4-73497565-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_001133.2(AFM):c.1192-87T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 759,300 control chromosomes in the GnomAD database, including 23,876 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 0.22 ( 4233 hom., cov: 32)

Exomes 𝑓: 0.25 ( 19643 hom. )

Consequence

AFM
NM_001133.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0960

Publications

2 publications found

Variant links:

Genes affected

AFM (HGNC:316): (afamin) This gene is a member of the albumin gene family, which is comprised of four genes that localize to chromosome 4 in a tandem arrangement. These four genes encode structurally-related serum transport proteins that are known to be evolutionarily related. The protein encoded by this gene is regulated developmentally, expressed in the liver and secreted into the bloodstream. [provided by RefSeq, Jul 2008]

AFM 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=-0.86).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
AFM	NM_001133.2 link	c.1192-87T>C	intron_variant	Intron 9 of 14	ENST00000226355.5	NP_001124.1
AFM	XM_017007842.3 link	c.1192-87T>C	intron_variant	Intron 9 of 12		XP_016863331.1
AFM	XM_017007843.3 link	c.1192-87T>C	intron_variant	Intron 9 of 10		XP_016863332.1
AFM	XM_017007844.3 link	c.1192-87T>C	intron_variant	Intron 9 of 10		XP_016863333.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AFM	ENST00000226355.5 link	c.1192-87T>C		intron_variant	Intron 9 of 14	1	NM_001133.2	ENSP00000226355.3
AFM	ENST00000505794.1 link	n.319-87T>C		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

AF:

0.224

AC:

33983

AN:

151996

Hom.:

4237

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.282

Gnomad AMR

AF:

0.333

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.325

Gnomad SAS

AF:

0.296

Gnomad FIN

AF:

0.231

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.238

Gnomad OTH

AF:

0.251

GnomAD4 exome

AF:

0.249

AC:

151333

AN:

607186

Hom.:

19643

AF XY:

0.250

AC XY:

77483

AN XY:

310166

show subpopulations

African (AFR)

AF:

0.123

AC:

1604

AN:

13034

American (AMR)

AF:

0.331

AC:

4156

AN:

12540

Ashkenazi Jewish (ASJ)

AF:

0.329

AC:

4493

AN:

13648

East Asian (EAS)

AF:

0.331

AC:

8747

AN:

26432

South Asian (SAS)

AF:

0.289

AC:

7920

AN:

27380

European-Finnish (FIN)

AF:

0.234

AC:

8384

AN:

35834

Middle Eastern (MID)

AF:

0.312

AC:

898

AN:

2874

European-Non Finnish (NFE)

AF:

0.241

AC:

107533

AN:

446204

Other (OTH)

AF:

0.260

AC:

7598

AN:

29240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

5422

10844

16265

21687

27109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2912

5824

8736

11648

14560

<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:

0.223

AC:

33984

AN:

152114

Hom.:

4233

Cov.:

AF XY:

0.228

AC XY:

16952

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.125

AC:

5198

AN:

41520

American (AMR)

AF:

0.333

AC:

5086

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.323

AC:

1120

AN:

3466

East Asian (EAS)

AF:

0.325

AC:

1683

AN:

5176

South Asian (SAS)

AF:

0.296

AC:

1429

AN:

4828

European-Finnish (FIN)

AF:

0.231

AC:

2440

AN:

10558

Middle Eastern (MID)

AF:

0.316

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.238

AC:

16149

AN:

67978

Other (OTH)

AF:

0.250

AC:

529

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1303

2607

3910

5214

6517

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

372

744

1116

1488

1860

<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:

0.228

Hom.:

998

Bravo

AF:

0.225

Asia WGS

AF:

0.307

AC:

1066

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

4.8

(source)

DANN

Benign

0.67

PhyloP100

0.096

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over