chr6-16274423-C-T

Variant names:

• chr6-16274423-C-T
• rs114417367
• NM_006877.4:c.474C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_006877.4(GMPR):​c.474C>T​(p.Asn158Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,595,210 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0076 (18 hom., cov: 32)
  • Exomes 𝑓: 0.00083 (12 hom.)
• Consequence: GMPR NM_006877.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.208
• Publications: 1 publications found

Genes affected

GMPR (HGNC:4376): (guanosine monophosphate reductase) This gene encodes an enzyme that catalyzes the irreversible and NADPH-dependent reductive deamination of GMP to IMP. The protein also functions in the re-utilization of free intracellular bases and purine nucleosides.[provided by RefSeq, Oct 2009]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 6-16274423-C-T is Benign according to our data. Variant chr6-16274423-C-T is described in ClinVar as Benign. ClinVar VariationId is 712612.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.208 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00761 (1158/152262) while in subpopulation AFR AF = 0.0261 (1084/41556). AF 95% confidence interval is 0.0248. There are 18 homozygotes in GnomAd4. There are 538 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006877.4. 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
	GMPR	NM_006877.4	MANE Select	c.474C>T	p.Asn158Asn	synonymous	Exon 5 of 9	NP_006868.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GMPR	ENST00000259727.5	TSL:1 MANE Select	c.474C>T	p.Asn158Asn	synonymous	Exon 5 of 9	ENSP00000259727.4	P36959
	GMPR	ENST00000864761.1		c.474C>T	p.Asn158Asn	synonymous	Exon 5 of 10	ENSP00000534820.1
	GMPR	ENST00000967431.1		c.567C>T	p.Asn189Asn	synonymous	Exon 6 of 10	ENSP00000637490.1

Frequencies

GnomAD3 genomes AF: 0.00760 AC: 1156 AN: 152144 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.0261

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00360

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00479

GnomAD2 exomes AF: 0.00228 AC: 572 AN: 251390 AF XY: 0.00171

Gnomad AFR exome AF: 0.0297

Gnomad AMR exome AF: 0.00159

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000176

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.000834 AC: 1204 AN: 1442948 Hom.: 12 Cov.: 27 AF XY: 0.000747 AC XY: 537 AN XY: 719012

African (AFR) AF: 0.0259 AC: 856 AN: 33050

American (AMR) AF: 0.00186 AC: 83 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26038

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39622

South Asian (SAS) AF: 0.0000582 AC: 5 AN: 85886

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.000699 AC: 4 AN: 5720

European-Non Finnish (NFE) AF: 0.000141 AC: 154 AN: 1094804

Other (OTH) AF: 0.00167 AC: 100 AN: 59726

GnomAD4 genome AF: 0.00761 AC: 1158 AN: 152262 Hom.: 18 Cov.: 32 AF XY: 0.00723 AC XY: 538 AN XY: 74448

African (AFR) AF: 0.0261 AC: 1084 AN: 41556

American (AMR) AF: 0.00360 AC: 55 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68014

Other (OTH) AF: 0.00474 AC: 10 AN: 2110

Alfa AF: 0.00273 Hom.: 4

Bravo AF: 0.00901

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

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	-0.30
CADD	Benign	8.0
DANN	Benign	0.67
PhyloP100		-0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=93/7	polymorphism

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: rs114417367; hg19: chr6-16274654;