dbSNP rs2287531: AFTPH:c.2271+4A>C (chr2-64569683-A-C) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP3BA1

The NM_203437.4(AFTPH):c.2271+4A>C variant causes a splice region, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00879 in 1,613,346 control chromosomes in the GnomAD database, including 621 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.024 ( 145 hom., cov: 33)

Exomes 𝑓: 0.0072 ( 476 hom. )

Consequence

AFTPH
NM_203437.4 splice_region, intron

Scores

Splicing: ADA: 0.9872

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.78

Publications

6 publications found

Variant links:

Genes affected

AFTPH (HGNC:25951): (aftiphilin) Enables clathrin binding activity. Predicted to be involved in intracellular transport. Located in Golgi apparatus; cytosol; and nucleoplasm. Part of AP-1 adaptor complex. [provided by Alliance of Genome Resources, Apr 2022]

AFTPH links:

LOC105374773 (HGNC:):

LOC105374773 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFTPH	NM_203437.4 link	c.2271+4A>C		splice_region_variant, intron_variant	Intron 5 of 9	ENST00000409933.6	NP_982261.2	Q6ULP2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AFTPH	ENST00000409933.6 link	c.2271+4A>C		splice_region_variant, intron_variant	Intron 5 of 9	1	NM_203437.4	ENSP00000387071.1		Q6ULP2-1

Frequencies

GnomAD3 genomes

AF:

0.0242

AC:

3682

AN:

152206

Hom.:

145

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0641

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00812

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.136

Gnomad SAS

AF:

0.00889

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00112

Gnomad OTH

AF:

0.0172

GnomAD2 exomes

AF:

0.0172

AC:

4312

AN:

250974

AF XY:

0.0154

show subpopulations

Gnomad AFR exome

AF:

0.0668

Gnomad AMR exome

AF:

0.00354

Gnomad ASJ exome

AF:

0.00457

Gnomad EAS exome

AF:

0.144

Gnomad FIN exome

AF:

0.00167

Gnomad NFE exome

AF:

0.00127

Gnomad OTH exome

AF:

0.00768

GnomAD4 exome

AF:

0.00719

AC:

10501

AN:

1461022

Hom.:

476

Cov.:

AF XY:

0.00701

AC XY:

5097

AN XY:

726846

show subpopulations

African (AFR)

AF:

0.0659

AC:

2204

AN:

33434

American (AMR)

AF:

0.00436

AC:

195

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00387

AC:

101

AN:

26110

East Asian (EAS)

AF:

0.136

AC:

5394

AN:

39570

South Asian (SAS)

AF:

0.00670

AC:

578

AN:

86234

European-Finnish (FIN)

AF:

0.00174

AC:

AN:

53354

Middle Eastern (MID)

AF:

0.0154

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000890

AC:

989

AN:

1111490

Other (OTH)

AF:

0.0142

AC:

858

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

466

932

1397

1863

2329

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

176

352

528

704

880

<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:

0.0242

AC:

3685

AN:

152324

Hom.:

145

Cov.:

AF XY:

0.0245

AC XY:

1827

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0640

AC:

2659

AN:

41566

American (AMR)

AF:

0.00810

AC:

124

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00576

AC:

AN:

3470

East Asian (EAS)

AF:

0.136

AC:

707

AN:

5184

South Asian (SAS)

AF:

0.00869

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00160

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00112

AC:

AN:

68026

Other (OTH)

AF:

0.0170

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

174

348

522

696

870

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.00869

Hom.:

Bravo

AF:

0.0271

EpiCase

AF:

0.00175

EpiControl

AF:

0.00107

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

(source)

DANN

Uncertain

0.98

PhyloP100

8.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Mutation Taster

=86/14

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.81

SpliceAI score (max)

0.060

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