19-19635342-G-T

Position:

• chr19-19635342-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016573.4(GMIP):​c.1560+73C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0874 in 1,563,630 control chromosomes in the GnomAD database, including 6,512 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 0.11 (1035 hom., cov: 32)
  • Exomes 𝑓: 0.085 (5477 hom.)
• Consequence: GMIP NM_016573.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203

Genes affected

GMIP (HGNC:24852): (GEM interacting protein) This gene encodes a member of the ARHGAP family of Rho/Rac/Cdc42-like GTPase activating proteins. The encoded protein interacts with the Ras-related protein Gem through its N-terminal domain. Separately, it interacts with RhoA through a RhoGAP domain, and stimulates RhoA-dependent GTPase activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ACMG classification

Verdict is Benign. Variant got -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 = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GMIP	NM_016573.4	c.1560+73C>A		intron_variant		ENST00000203556.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GMIP	ENST00000203556.9	c.1560+73C>A		intron_variant		1	NM_016573.4	P1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16466 AN: 152070 Hom.: 1023 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.0527

Gnomad EAS AF: 0.0573

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0749

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0792

Gnomad OTH AF: 0.0940

GnomAD4 exome AF: 0.0851 AC: 120151 AN: 1411442 Hom.: 5477 Cov.: 28 AF XY: 0.0849 AC XY: 59353 AN XY: 698988

Gnomad4 AFR exome AF: 0.173

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.0597

Gnomad4 EAS exome AF: 0.0594

Gnomad4 SAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.0765

Gnomad4 NFE exome AF: 0.0808

Gnomad4 OTH exome AF: 0.0832

GnomAD4 genome AF: 0.108 AC: 16505 AN: 152188 Hom.: 1035 Cov.: 32 AF XY: 0.109 AC XY: 8114 AN XY: 74410

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.0527

Gnomad4 EAS AF: 0.0573

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.0749

Gnomad4 NFE AF: 0.0792

Gnomad4 OTH AF: 0.103

Alfa AF: 0.0791 Hom.: 706

Bravo AF: 0.113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.6
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs2304128; hg19: chr19-19746151;