rs17029542

Positions:

• chr4-99828193-G-A
• chr4-99828193-G-T

Variant summary

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

The NM_014395.3(DAPP1):​c.102-7430G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0477 in 152,236 control chromosomes in the GnomAD database, including 325 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 0.048 (325 hom., cov: 32)
• Consequence: DAPP1 NM_014395.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.893

Genes affected

DAPP1 (HGNC:16500): (dual adaptor of phosphotyrosine and 3-phosphoinositides 1) Enables phosphatidylinositol-3,4,5-trisphosphate binding activity and phosphatidylinositol-3,4-bisphosphate binding activity. Predicted to be involved in signal transduction. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAPP1	NM_014395.3	c.102-7430G>A		intron_variant		ENST00000512369.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAPP1	ENST00000512369.2	c.102-7430G>A		intron_variant		1	NM_014395.3	P1
DAPP1	ENST00000296414.11	c.102-7430G>A		intron_variant		1
DAPP1	ENST00000507994.1	n.166-7430G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0477 AC: 7255 AN: 152116 Hom.: 324 Cov.: 32

Gnomad AFR AF: 0.0569

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0665

Gnomad ASJ AF: 0.0426

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.0528

Gnomad FIN AF: 0.0544

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0226

Gnomad OTH AF: 0.0358

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

GnomAD4 genome AF: 0.0477 AC: 7259 AN: 152236 Hom.: 325 Cov.: 32 AF XY: 0.0508 AC XY: 3783 AN XY: 74442

Gnomad4 AFR AF: 0.0570

Gnomad4 AMR AF: 0.0664

Gnomad4 ASJ AF: 0.0426

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.0522

Gnomad4 FIN AF: 0.0544

Gnomad4 NFE AF: 0.0226

Gnomad4 OTH AF: 0.0345

Alfa AF: 0.0113 Hom.: 5

Bravo AF: 0.0519

Asia WGS AF: 0.165 AC: 573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.14
DANN	Benign	0.71

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: rs17029542; hg19: chr4-100749350;