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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001133.2. 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
	AFM	NM_001133.2	MANE Select	c.1192-87T>C		intron	N/A	NP_001124.1	P43652

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AFM	ENST00000226355.5	TSL:1 MANE Select	c.1192-87T>C	intron	N/A	ENSP00000226355.3	P43652
AFM	ENST00000853605.1		c.1192-87T>C	intron	N/A	ENSP00000523664.1
AFM	ENST00000853610.1		c.1192-87T>C	intron	N/A	ENSP00000523669.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over