2-64572292-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_203437.4(AFTPH):c.2272-654A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0521 in 151,968 control chromosomes in the GnomAD database, including 465 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 0.052 (465 hom., cov: 32)
• Consequence: AFTPH NM_203437.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140

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]

LOC105374773 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AFTPH	NM_203437.4	c.2272-654A>T		intron_variant		ENST00000409933.6
LOC105374773	XR_007086343.1	n.613+8856T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFTPH	ENST00000409933.6	c.2272-654A>T		intron_variant		1	NM_203437.4	A1

Frequencies

GnomAD3 genomes AF: 0.0519 AC: 7876 AN: 151864 Hom.: 457 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0692

Gnomad ASJ AF: 0.0300

Gnomad EAS AF: 0.0632

Gnomad SAS AF: 0.0423

Gnomad FIN AF: 0.00391

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00263

Gnomad OTH AF: 0.0431

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0521 AC: 7910 AN: 151968 Hom.: 465 Cov.: 32 AF XY: 0.0511 AC XY: 3792 AN XY: 74258

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.0696

Gnomad4 ASJ AF: 0.0300

Gnomad4 EAS AF: 0.0632

Gnomad4 SAS AF: 0.0418

Gnomad4 FIN AF: 0.00391

Gnomad4 NFE AF: 0.00263

Gnomad4 OTH AF: 0.0427

Alfa AF: 0.0286 Hom.: 36

Bravo AF: 0.0642

Asia WGS AF: 0.0770 AC: 268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.9
Dann	Benign	0.81

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

LitVar

Other links and lift over

dbSNP: rs10496121; hg19: chr2-64799426;