rs4776908

Positions:

• chr15-67247749-T-C
• chr15-67247749-T-G

Variant summary

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

The NM_024666.5(AAGAB):​c.73+6810A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,228 control chromosomes in the GnomAD database, including 4,232 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 (4232 hom., cov: 32)
• Consequence: AAGAB NM_024666.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AAGAB	NM_024666.5	c.73+6810A>G		intron_variant		ENST00000261880.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AAGAB	ENST00000261880.10	c.73+6810A>G		intron_variant		1	NM_024666.5	P1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32883 AN: 152110 Hom.: 4218 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.216 AC: 32934 AN: 152228 Hom.: 4232 Cov.: 32 AF XY: 0.221 AC XY: 16426 AN XY: 74436

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.483

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.261

Alfa AF: 0.207 Hom.: 585

Bravo AF: 0.224

Asia WGS AF: 0.402 AC: 1396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.30
DANN	Benign	0.42

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: rs4776908; hg19: chr15-67540087;