Genetic Variant AMFR:c.1380+203C>T (chr16-56385716-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001144.6(AMFR):c.1380+203C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 572,058 control chromosomes in the GnomAD database, including 90,516 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.60 ( 28272 hom., cov: 30)

Exomes 𝑓: 0.54 ( 62244 hom. )

Consequence

AMFR
NM_001144.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.116

Publications

23 publications found

Variant links:

Genes affected

AMFR (HGNC:463): (autocrine motility factor receptor) This locus encodes a glycosylated transmembrane receptor. Its ligand, autocrine motility factor, is a tumor motility-stimulating protein secreted by tumor cells. The encoded receptor is also a member of the E3 ubiquitin ligase family of proteins. It catalyzes ubiquitination and endoplasmic reticulum-associated degradation of specific proteins. [provided by RefSeq, Feb 2012]

AMFR Gene-Disease associations (from GenCC):

spastic paraplegia 89, autosomal recessive
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P

AMFR 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=-0.77).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
AMFR	NM_001144.6	MANE Select	c.1380+203C>T	intron	N/A	NP_001135.3
AMFR	NM_001323512.2		c.1476+203C>T	intron	N/A	NP_001310441.1
AMFR	NM_001323511.2		c.1095+203C>T	intron	N/A	NP_001310440.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AMFR	ENST00000290649.10	TSL:1 MANE Select	c.1380+203C>T	intron	N/A	ENSP00000290649.5	Q9UKV5
AMFR	ENST00000861442.1		c.1380+203C>T	intron	N/A	ENSP00000531501.1
AMFR	ENST00000861443.1		c.1380+203C>T	intron	N/A	ENSP00000531502.1

Frequencies

GnomAD3 genomes

AF:

0.595

AC:

90207

AN:

151484

Hom.:

28237

Cov.:

show subpopulations

Gnomad AFR

AF:

0.790

Gnomad AMI

AF:

0.583

Gnomad AMR

AF:

0.553

Gnomad ASJ

AF:

0.531

Gnomad EAS

AF:

0.438

Gnomad SAS

AF:

0.606

Gnomad FIN

AF:

0.394

Gnomad MID

AF:

0.471

Gnomad NFE

AF:

0.534

Gnomad OTH

AF:

0.572

GnomAD4 exome

AF:

0.539

AC:

226624

AN:

420456

Hom.:

62244

Cov.:

AF XY:

0.544

AC XY:

120224

AN XY:

221126

show subpopulations

African (AFR)

AF:

0.784

AC:

9285

AN:

11844

American (AMR)

AF:

0.556

AC:

9811

AN:

17646

Ashkenazi Jewish (ASJ)

AF:

0.530

AC:

6780

AN:

12804

East Asian (EAS)

AF:

0.495

AC:

14488

AN:

29250

South Asian (SAS)

AF:

0.612

AC:

25634

AN:

41854

European-Finnish (FIN)

AF:

0.400

AC:

10843

AN:

27078

Middle Eastern (MID)

AF:

0.563

AC:

1039

AN:

1844

European-Non Finnish (NFE)

AF:

0.534

AC:

135492

AN:

253802

Other (OTH)

AF:

0.545

AC:

13252

AN:

24334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

4716

9431

14147

18862

23578

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

748

1496

2244

2992

3740

<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:

0.596

AC:

90287

AN:

151602

Hom.:

28272

Cov.:

AF XY:

0.589

AC XY:

43596

AN XY:

73976

show subpopulations

African (AFR)

AF:

0.789

AC:

32658

AN:

41374

American (AMR)

AF:

0.553

AC:

8425

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.531

AC:

1838

AN:

3464

East Asian (EAS)

AF:

0.437

AC:

2245

AN:

5132

South Asian (SAS)

AF:

0.607

AC:

2914

AN:

4802

European-Finnish (FIN)

AF:

0.394

AC:

4105

AN:

10414

Middle Eastern (MID)

AF:

0.472

AC:

137

AN:

290

European-Non Finnish (NFE)

AF:

0.534

AC:

36242

AN:

67868

Other (OTH)

AF:

0.568

AC:

1194

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1698

3395

5093

6790

8488

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

742

1484

2226

2968

3710

<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:

0.584

Hom.:

5248

Bravo

AF:

0.614

Asia WGS

AF:

0.550

AC:

1913

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

4.3

(source)

DANN

Benign

0.82

PhyloP100

0.12

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