rs72816449

Variant names:

• chr5-145859720-C-G
• rs72816449
• NM_001080516.2:c.*13G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-145859720-C-G
• chr5-145859720-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001080516.2(GRXCR2):​c.*13G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.036 in 1,613,454 control chromosomes in the GnomAD database, including 1,304 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.028 (105 hom., cov: 32)
  • Exomes 𝑓: 0.037 (1199 hom.)
• Consequence: GRXCR2 NM_001080516.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.206
• Publications: 3 publications found

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]

GRXCR2 Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 101

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-145859720-C-G is Benign according to our data. Variant chr5-145859720-C-G is described in ClinVar as Benign. ClinVar VariationId is 1261199.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0277 (4219/152210) while in subpopulation NFE AF = 0.0415 (2822/67990). AF 95% confidence interval is 0.0402. There are 105 homozygotes in GnomAd4. There are 2091 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 105 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080516.2. 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
	GRXCR2	NM_001080516.2	MANE Select	c.*13G>C		3_prime_UTR	Exon 3 of 3	NP_001073985.1	A6NFK2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRXCR2	ENST00000377976.3	TSL:2 MANE Select	c.*13G>C		3_prime_UTR	Exon 3 of 3	ENSP00000367214.1	A6NFK2
	GRXCR2	ENST00000639411.1	TSL:5	c.*13G>C		3_prime_UTR	Exon 4 of 4	ENSP00000491860.1	A0A1W2PQQ7

Frequencies

GnomAD3 genomes AF: 0.0277 AC: 4219 AN: 152092 Hom.: 105 Cov.: 32

Gnomad AFR AF: 0.00659

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0191

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00871

Gnomad FIN AF: 0.0628

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0415

Gnomad OTH AF: 0.0278

GnomAD2 exomes AF: 0.0288 AC: 7238 AN: 250908 AF XY: 0.0292

Gnomad AFR exome AF: 0.00629

Gnomad AMR exome AF: 0.0119

Gnomad ASJ exome AF: 0.0119

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0584

Gnomad NFE exome AF: 0.0432

Gnomad OTH exome AF: 0.0311

GnomAD4 exome AF: 0.0369 AC: 53912 AN: 1461244 Hom.: 1199 Cov.: 31 AF XY: 0.0362 AC XY: 26312 AN XY: 726944

African (AFR) AF: 0.00618 AC: 207 AN: 33470

American (AMR) AF: 0.0129 AC: 575 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.0119 AC: 312 AN: 26118

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39686

South Asian (SAS) AF: 0.00913 AC: 787 AN: 86240

European-Finnish (FIN) AF: 0.0585 AC: 3122 AN: 53412

Middle Eastern (MID) AF: 0.00936 AC: 54 AN: 5768

European-Non Finnish (NFE) AF: 0.0423 AC: 47017 AN: 1111470

Other (OTH) AF: 0.0303 AC: 1832 AN: 60380

GnomAD4 genome AF: 0.0277 AC: 4219 AN: 152210 Hom.: 105 Cov.: 32 AF XY: 0.0281 AC XY: 2091 AN XY: 74422

African (AFR) AF: 0.00657 AC: 273 AN: 41558

American (AMR) AF: 0.0190 AC: 291 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3470

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5170

South Asian (SAS) AF: 0.00872 AC: 42 AN: 4818

European-Finnish (FIN) AF: 0.0628 AC: 665 AN: 10594

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0415 AC: 2822 AN: 67990

Other (OTH) AF: 0.0275 AC: 58 AN: 2112

Alfa AF: 0.0302 Hom.: 18

Bravo AF: 0.0246

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.8
DANN	Benign	0.48
PhyloP100		-0.21
Mutation Taster		=99/1	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs72816449; hg19: chr5-145239283;