chr17-29582334-C-T

Variant names:

• chr17-29582334-C-T
• rs894606
• NM_014030.4:c.406-190G>A

Variant summary

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

The NM_014030.4(GIT1):​c.406-190G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 152,224 control chromosomes in the GnomAD database, including 11,325 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 0.36 (11325 hom., cov: 33)
• Consequence: GIT1 NM_014030.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.657
• Publications: 20 publications found

Genes affected

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]

TP53I13 (HGNC:25102): (tumor protein p53 inducible protein 13) Involved in several processes, including negative regulation of cell cycle; response to UV; and response to xenobiotic stimulus. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ABHD15-AS1 (HGNC:49685): (ABHD15 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIT1	NM_014030.4	c.406-190G>A		intron_variant	Intron 4 of 19	ENST00000225394.8	NP_054749.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIT1	ENST00000225394.8	c.406-190G>A		intron_variant	Intron 4 of 19	1	NM_014030.4	ENSP00000225394.3

Frequencies

GnomAD3 genomes AF: 0.362 AC: 55011 AN: 152106 Hom.: 11318 Cov.: 33

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.361 AC: 55025 AN: 152224 Hom.: 11325 Cov.: 33 AF XY: 0.369 AC XY: 27457 AN XY: 74416

African (AFR) AF: 0.154 AC: 6380 AN: 41548

American (AMR) AF: 0.408 AC: 6242 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1692 AN: 3470

East Asian (EAS) AF: 0.646 AC: 3346 AN: 5178

South Asian (SAS) AF: 0.438 AC: 2114 AN: 4828

European-Finnish (FIN) AF: 0.449 AC: 4753 AN: 10586

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29189 AN: 68012

Other (OTH) AF: 0.389 AC: 824 AN: 2116

Alfa AF: 0.410 Hom.: 54032

Bravo AF: 0.351

Asia WGS AF: 0.484 AC: 1686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.7
DANN	Benign	0.86
PhyloP100		0.66
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: rs894606; hg19: chr17-27909352;