chr4-99822356-T-G

Variant names:

• chr4-99822356-T-G
• rs3775500
• NM_014395.3:c.101+5342T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014395.3(DAPP1):​c.101+5342T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 151,860 control chromosomes in the GnomAD database, including 8,511 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 0.32 (8511 hom., cov: 31)
• Consequence: DAPP1 NM_014395.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014395.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAPP1	NM_014395.3	MANE Select	c.101+5342T>G		intron	N/A	NP_055210.2
	DAPP1	NM_001306151.2		c.101+5342T>G		intron	N/A	NP_001293080.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAPP1	ENST00000512369.2	TSL:1 MANE Select	c.101+5342T>G		intron	N/A	ENSP00000423602.1
	DAPP1	ENST00000296414.11	TSL:1	c.101+5342T>G		intron	N/A	ENSP00000296414.7
	DAPP1	ENST00000507994.1	TSL:2	n.165+5342T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49259 AN: 151740 Hom.: 8495 Cov.: 31

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.325 AC: 49315 AN: 151860 Hom.: 8511 Cov.: 31 AF XY: 0.323 AC XY: 23964 AN XY: 74228

African (AFR) AF: 0.445 AC: 18419 AN: 41400

American (AMR) AF: 0.324 AC: 4947 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1329 AN: 3470

East Asian (EAS) AF: 0.410 AC: 2105 AN: 5136

South Asian (SAS) AF: 0.214 AC: 1032 AN: 4814

European-Finnish (FIN) AF: 0.300 AC: 3161 AN: 10540

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17258 AN: 67930

Other (OTH) AF: 0.320 AC: 674 AN: 2108

Alfa AF: 0.289 Hom.: 18295

Bravo AF: 0.337

Asia WGS AF: 0.355 AC: 1233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.0
DANN	Benign	0.40
PhyloP100		-0.036
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

Other links and lift over

dbSNP: rs3775500; hg19: chr4-100743513;