rs4776908

Variant names:

• chr15-67247749-T-C
• rs4776908
• NM_024666.5:c.73+6810A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

AAGAB Gene-Disease associations (from GenCC):

• palmoplantar keratoderma, punctate type 1A

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics
• punctate palmoplantar keratoderma type 1

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024666.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AAGAB	NM_024666.5	MANE Select	c.73+6810A>G		intron	N/A	NP_078942.3
	AAGAB	NM_001271885.2		c.-255+7388A>G		intron	N/A	NP_001258814.1	Q6PD74-2
	AAGAB	NM_001271886.2		c.-255+6665A>G		intron	N/A	NP_001258815.1	Q6PD74-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AAGAB	ENST00000261880.10	TSL:1 MANE Select	c.73+6810A>G		intron	N/A	ENSP00000261880.5	Q6PD74-1
	AAGAB	ENST00000947778.1		c.73+6810A>G		intron	N/A	ENSP00000617837.1
	AAGAB	ENST00000902812.1		c.73+6810A>G		intron	N/A	ENSP00000572871.1

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

African (AFR) AF: 0.105 AC: 4372 AN: 41524

American (AMR) AF: 0.329 AC: 5029 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1266 AN: 3472

East Asian (EAS) AF: 0.483 AC: 2503 AN: 5178

South Asian (SAS) AF: 0.299 AC: 1447 AN: 4834

European-Finnish (FIN) AF: 0.181 AC: 1920 AN: 10598

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15558 AN: 68014

Other (OTH) AF: 0.261 AC: 551 AN: 2112

Alfa AF: 0.204 Hom.: 592

Bravo AF: 0.224

Asia WGS AF: 0.402 AC: 1396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.30
DANN	Benign	0.42
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4776908;

hg19: chr15-67540087;