17-29590753-A-G

Position:

• chr17-29590753-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000583413.4(GIT1):​c.88+3189T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 151,772 control chromosomes in the GnomAD database, including 32,504 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 0.65 (32504 hom., cov: 30)
• Consequence: GIT1 ENST00000583413.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98

Genes affected

ANKRD13B (HGNC:):

GIT1 (HGNC:4272): (GIT ArfGAP 1) Enables gamma-tubulin binding activity. Involved in positive regulation of microtubule nucleation and regulation of cytokinesis. Located in several cellular components, including focal adhesion; microtubule cytoskeleton; and mitochondrion. Implicated in attention deficit hyperactivity disorder. Biomarker of Huntington's disease. [provided by Alliance of Genome Resources, Apr 2022]

ANKRD13B (HGNC:26363): (ankyrin repeat domain 13B) Enables ubiquitin-dependent protein binding activity. Involved in negative regulation of receptor internalization. Located in endosome; perinuclear region of cytoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.29590753A>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD13B	ENST00000487527.5	n.80+891A>G		intron_variant		1
GIT1	ENST00000583413.4	c.88+3189T>C		intron_variant		4		ENSP00000466824.1
ANKRD13B	ENST00000583728.5	c.-283+891A>G		intron_variant		4		ENSP00000467078.1
ABHD15-AS1	ENST00000581474.1	n.153+30054A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99038 AN: 151654 Hom.: 32471 Cov.: 30

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.646

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

GnomAD4 genome AF: 0.653 AC: 99110 AN: 151772 Hom.: 32504 Cov.: 30 AF XY: 0.651 AC XY: 48306 AN XY: 74152

Gnomad4 AFR AF: 0.620

Gnomad4 AMR AF: 0.641

Gnomad4 ASJ AF: 0.710

Gnomad4 EAS AF: 0.759

Gnomad4 SAS AF: 0.643

Gnomad4 FIN AF: 0.592

Gnomad4 NFE AF: 0.676

Gnomad4 OTH AF: 0.648

Alfa AF: 0.672 Hom.: 38770

Bravo AF: 0.654

Asia WGS AF: 0.684 AC: 2382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Benign	0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3110496; hg19: chr17-27917771;