19-34275683-G-A

Variant names:

• chr19-34275683-G-A
• rs10407640
• NM_014686.5:c.-796+21069G>A

Variant summary

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

The NM_014686.5(GARRE1):​c.-796+21069G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 152,130 control chromosomes in the GnomAD database, including 46,235 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 0.77 (46235 hom., cov: 32)
• Consequence: GARRE1 NM_014686.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.526
• Publications: 12 publications found

Genes affected

GARRE1 (HGNC:29016): (granule associated Rac and RHOG effector 1) Enables CCR4-NOT complex binding activity and small GTPase binding activity. Involved in Rac protein signal transduction. Located in P-body. [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=-1.06).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GARRE1	NM_014686.5	c.-796+21069G>A		intron_variant	Intron 1 of 13	ENST00000299505.8	NP_055501.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GARRE1	ENST00000299505.8	c.-796+21069G>A		intron_variant	Intron 1 of 13	1	NM_014686.5	ENSP00000299505.4

Frequencies

GnomAD3 genomes AF: 0.774 AC: 117712 AN: 152012 Hom.: 46184 Cov.: 32

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.806

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.785

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.776

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

GnomAD4 genome AF: 0.774 AC: 117820 AN: 152130 Hom.: 46235 Cov.: 32 AF XY: 0.772 AC XY: 57426 AN XY: 74354

African (AFR) AF: 0.823 AC: 34156 AN: 41512

American (AMR) AF: 0.806 AC: 12321 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.784 AC: 2720 AN: 3470

East Asian (EAS) AF: 0.367 AC: 1893 AN: 5162

South Asian (SAS) AF: 0.786 AC: 3788 AN: 4818

European-Finnish (FIN) AF: 0.749 AC: 7904 AN: 10554

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.771 AC: 52448 AN: 68008

Other (OTH) AF: 0.777 AC: 1639 AN: 2110

Alfa AF: 0.767 Hom.: 81113

Bravo AF: 0.778

Asia WGS AF: 0.613 AC: 2132 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.56
DANN	Benign	0.44
PhyloP100		-0.53
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: rs10407640; hg19: chr19-34766588;