chr15-67209254-C-T

Position:

• chr15-67209254-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_024666.5(AAGAB):​c.618+208G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,094 control chromosomes in the GnomAD database, including 4,055 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (4055 hom., cov: 33)
• Consequence: AAGAB NM_024666.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.09

Genes affected

AAGAB (HGNC:25662): (alpha and gamma adaptin binding protein) The protein encoded by this gene interacts with the gamma-adaptin and alpha-adaptin subunits of complexes involved in clathrin-coated vesicle trafficking. Mutations in this gene are associated with type I punctate palmoplantar keratoderma. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2012]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 15-67209254-C-T is Benign according to our data. Variant chr15-67209254-C-T is described in ClinVar as [Benign]. Clinvar id is 1237371.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AAGAB	NM_024666.5	c.618+208G>A		intron_variant		ENST00000261880.10
AAGAB	NM_001271885.2	c.291+208G>A		intron_variant
AAGAB	NM_001271886.2	c.291+208G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AAGAB	ENST00000261880.10	c.618+208G>A		intron_variant		1	NM_024666.5	P1
AAGAB	ENST00000542650.5	c.291+208G>A		intron_variant		2
AAGAB	ENST00000561452.5	c.291+208G>A		intron_variant		5
AAGAB	ENST00000538028.1	n.299+208G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31779 AN: 151976 Hom.: 4053 Cov.: 33

Gnomad AFR AF: 0.0841

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.209 AC: 31797 AN: 152094 Hom.: 4055 Cov.: 33 AF XY: 0.214 AC XY: 15900 AN XY: 74358

Gnomad4 AFR AF: 0.0840

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.247

Alfa AF: 0.217 Hom.: 785

Bravo AF: 0.215

Asia WGS AF: 0.343 AC: 1194 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.20
DANN	Benign	0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs16953610; hg19: chr15-67501592;