5-145866186-A-T

Position:

• chr5-145866186-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001080516.2(GRXCR2):​c.564+315T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 150,822 control chromosomes in the GnomAD database, including 30,019 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.63 (30019 hom., cov: 29)
• Consequence: GRXCR2 NM_001080516.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.673

Genes affected

GRXCR2 (HGNC:33862): (glutaredoxin and cysteine rich domain containing 2) This gene encodes a protein containing a glutaredoxin domain, which functions in protein S-glutathionylation. A mutation in this gene was found in a family with autoosomal recessive nonsyndromic sensorineural deafness-101. [provided by RefSeq, Jun 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 5-145866186-A-T is Benign according to our data. Variant chr5-145866186-A-T is described in ClinVar as [Benign]. Clinvar id is 1260395.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRXCR2	NM_001080516.2	c.564+315T>A		intron_variant		ENST00000377976.3	NP_001073985.1
GRXCR2	XM_017009708.2	c.276+315T>A		intron_variant			XP_016865197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRXCR2	ENST00000377976.3	c.564+315T>A		intron_variant		2	NM_001080516.2	ENSP00000367214.1
GRXCR2	ENST00000639411.1	c.159+315T>A		intron_variant		5		ENSP00000491860.1

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94216 AN: 150722 Hom.: 29988 Cov.: 29

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.608

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

GnomAD4 genome AF: 0.625 AC: 94300 AN: 150822 Hom.: 30019 Cov.: 29 AF XY: 0.630 AC XY: 46428 AN XY: 73670

Gnomad4 AFR AF: 0.710

Gnomad4 AMR AF: 0.684

Gnomad4 ASJ AF: 0.599

Gnomad4 EAS AF: 0.728

Gnomad4 SAS AF: 0.706

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.613

Alfa AF: 0.461 Hom.: 1255

Bravo AF: 0.633

Asia WGS AF: 0.730 AC: 2534 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.9
DANN	Benign	0.66

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: rs2569007; hg19: chr5-145245749;