rs4766646

Variant names:

• chr12-109960340-T-A
• rs4766646
• NM_057169.5:c.988-382A>T

Your query was ambiguous. Multiple possible variants found:

• chr12-109960340-T-A
• chr12-109960340-T-C
• chr12-109960340-T-G

Variant summary

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

The NM_057169.5(GIT2):​c.988-382A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 152,208 control chromosomes in the GnomAD database, including 41,594 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 0.73 (41594 hom., cov: 33)
• Consequence: GIT2 NM_057169.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.581
• Publications: 9 publications found

Genes affected

GIT2 (HGNC:4273): (GIT ArfGAP 2) This gene encodes a member of the GIT protein family, which interact with G protein-coupled receptor kinases and possess ADP-ribosylation factor (ARF) GTPase-activating protein (GAP) activity. GIT proteins traffic between cytoplasmic complexes, focal adhesions, and the cell periphery, and interact with Pak interacting exchange factor beta (PIX) to form large oligomeric complexes that transiently recruit other proteins. GIT proteins regulate cytoskeletal dynamics and participate in receptor internalization and membrane trafficking. This gene has been shown to repress lamellipodial extension and focal adhesion turnover, and is thought to regulate cell motility. This gene undergoes extensive alternative splicing to generate multiple isoforms, but the full-length nature of some of these variants has not been determined. The various isoforms have functional differences, with respect to ARF GAP activity and to G protein-coupled receptor kinase 2 binding. [provided by RefSeq, Sep 2008]

TCHP (HGNC:28135): (trichoplein keratin filament binding) Involved in apoptotic process; negative regulation of cell growth; and negative regulation of cilium assembly. Located in several cellular components, including apical cortex; cytoskeleton; and mitochondrion. [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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_057169.5. 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
	GIT2	NM_057169.5	MANE Select	c.988-382A>T		intron	N/A	NP_476510.1	Q14161-1
	GIT2	NM_001135214.3		c.988-382A>T		intron	N/A	NP_001128686.1	Q14161-5
	GIT2	NM_001330153.2		c.985-382A>T		intron	N/A	NP_001317082.1	F8VXI9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIT2	ENST00000355312.8	TSL:1 MANE Select	c.988-382A>T		intron	N/A	ENSP00000347464.3	Q14161-1
	GIT2	ENST00000457474.6	TSL:1	c.994-382A>T		intron	N/A	ENSP00000391813.2	Q14161-10
	GIT2	ENST00000547815.5	TSL:1	c.988-382A>T		intron	N/A	ENSP00000450348.1	Q14161-2

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110518 AN: 152088 Hom.: 41523 Cov.: 33

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.799

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.694

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

GnomAD4 genome AF: 0.727 AC: 110655 AN: 152208 Hom.: 41594 Cov.: 33 AF XY: 0.728 AC XY: 54169 AN XY: 74416

African (AFR) AF: 0.895 AC: 37196 AN: 41550

American (AMR) AF: 0.754 AC: 11524 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1867 AN: 3472

East Asian (EAS) AF: 0.339 AC: 1754 AN: 5174

South Asian (SAS) AF: 0.799 AC: 3856 AN: 4826

European-Finnish (FIN) AF: 0.702 AC: 7423 AN: 10570

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.660 AC: 44879 AN: 68008

Other (OTH) AF: 0.694 AC: 1467 AN: 2114

Alfa AF: 0.593 Hom.: 1643

Bravo AF: 0.730

Asia WGS AF: 0.658 AC: 2291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.38
DANN	Benign	0.66
PhyloP100		-0.58
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: rs4766646; hg19: chr12-110398145;