17-29574957-A-G

Variant names:

• chr17-29574957-A-G
• rs550818
• NM_014030.4:c.2074-43T>C

Variant summary

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

The NM_014030.4(GIT1):​c.2074-43T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 1,502,650 control chromosomes in the GnomAD database, including 415,737 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 0.76 (43822 hom., cov: 31)
  • Exomes 𝑓: 0.74 (371915 hom.)
• Consequence: GIT1 NM_014030.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.512
• Publications: 19 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]

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

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=9.3827845E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014030.4. 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
	GIT1	NM_014030.4	MANE Select	c.2074-43T>C		intron	N/A	NP_054749.2
	GIT1	NM_001085454.2		c.2101-43T>C		intron	N/A	NP_001078923.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIT1	ENST00000225394.8	TSL:1 MANE Select	c.2074-43T>C		intron	N/A	ENSP00000225394.3
	GIT1	ENST00000394869.7	TSL:1	c.2101-43T>C		intron	N/A	ENSP00000378338.3
	GIT1	ENST00000473217.5	TSL:1	n.2023-43T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.757 AC: 114922 AN: 151868 Hom.: 43774 Cov.: 31

Gnomad AFR AF: 0.814

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.794

Gnomad EAS AF: 0.922

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.730

Gnomad OTH AF: 0.757

GnomAD2 exomes AF: 0.745 AC: 128282 AN: 172080 AF XY: 0.743

Gnomad AFR exome AF: 0.812

Gnomad AMR exome AF: 0.723

Gnomad ASJ exome AF: 0.795

Gnomad EAS exome AF: 0.919

Gnomad FIN exome AF: 0.673

Gnomad NFE exome AF: 0.729

Gnomad OTH exome AF: 0.745

GnomAD4 exome AF: 0.741 AC: 1000666 AN: 1350664 Hom.: 371915 Cov.: 22 AF XY: 0.739 AC XY: 491907 AN XY: 665250

African (AFR) AF: 0.815 AC: 25056 AN: 30750

American (AMR) AF: 0.725 AC: 25514 AN: 35192

Ashkenazi Jewish (ASJ) AF: 0.789 AC: 18316 AN: 23226

East Asian (EAS) AF: 0.917 AC: 33354 AN: 36388

South Asian (SAS) AF: 0.723 AC: 56526 AN: 78158

European-Finnish (FIN) AF: 0.671 AC: 31564 AN: 47048

Middle Eastern (MID) AF: 0.728 AC: 3998 AN: 5494

European-Non Finnish (NFE) AF: 0.736 AC: 764732 AN: 1038516

Other (OTH) AF: 0.744 AC: 41606 AN: 55892

GnomAD4 genome AF: 0.757 AC: 115019 AN: 151986 Hom.: 43822 Cov.: 31 AF XY: 0.755 AC XY: 56109 AN XY: 74272

African (AFR) AF: 0.814 AC: 33749 AN: 41456

American (AMR) AF: 0.738 AC: 11259 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.794 AC: 2752 AN: 3468

East Asian (EAS) AF: 0.922 AC: 4753 AN: 5156

South Asian (SAS) AF: 0.720 AC: 3466 AN: 4814

European-Finnish (FIN) AF: 0.667 AC: 7047 AN: 10560

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.730 AC: 49603 AN: 67950

Other (OTH) AF: 0.757 AC: 1599 AN: 2112

Alfa AF: 0.743 Hom.: 74438

Bravo AF: 0.766

TwinsUK AF: 0.736 AC: 2729

ALSPAC AF: 0.751 AC: 2894

ESP6500AA AF: 0.809 AC: 3535

ESP6500EA AF: 0.740 AC: 6321

ExAC AF: 0.705 AC: 81475

Asia WGS AF: 0.815 AC: 2836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.065
DANN	Benign	0.27
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.19	T
MetaRNN	Benign	9.4e-7	T
PhyloP100		-0.51
Vest4		0.040
GERP RS		-7.4
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs550818; hg19: chr17-27901975; COSMIC: COSV56403500; COSMIC: COSV56403500;