chr4-89247731-G-A

Variant names:

• chr4-89247731-G-A
• rs13115988
• NM_198281.3:c.*49C>T

Variant summary

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

The NM_198281.3(GPRIN3):​c.*49C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 1,516,038 control chromosomes in the GnomAD database, including 107,174 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 0.39 (12097 hom., cov: 32)
  • Exomes 𝑓: 0.36 (95077 hom.)
• Consequence: GPRIN3 NM_198281.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750
• Publications: 9 publications found

Genes affected

GPRIN3 (HGNC:27733): (GPRIN family member 3) Predicted to be involved in neuron projection development. Predicted to be active in plasma membrane. [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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPRIN3	NM_198281.3	c.*49C>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000609438.2	NP_938022.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPRIN3	ENST00000609438.2	c.*49C>T		3_prime_UTR_variant	Exon 2 of 2	2	NM_198281.3	ENSP00000476603.1
GPRIN3	ENST00000333209.4	c.*49C>T		3_prime_UTR_variant	Exon 1 of 1	6		ENSP00000328672.3
GPRIN3	ENST00000715382.1	c.*49C>T		3_prime_UTR_variant	Exon 2 of 2			ENSP00000520450.1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59111 AN: 151804 Hom.: 12069 Cov.: 32

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.378

GnomAD2 exomes AF: 0.415 AC: 81714 AN: 196954 AF XY: 0.412

Gnomad AFR exome AF: 0.430

Gnomad AMR exome AF: 0.521

Gnomad ASJ exome AF: 0.265

Gnomad EAS exome AF: 0.624

Gnomad FIN exome AF: 0.398

Gnomad NFE exome AF: 0.328

Gnomad OTH exome AF: 0.381

GnomAD4 exome AF: 0.364 AC: 496492 AN: 1364116 Hom.: 95077 Cov.: 24 AF XY: 0.368 AC XY: 246774 AN XY: 670566

African (AFR) AF: 0.430 AC: 13173 AN: 30656

American (AMR) AF: 0.515 AC: 18184 AN: 35340

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 5501 AN: 21260

East Asian (EAS) AF: 0.637 AC: 24728 AN: 38840

South Asian (SAS) AF: 0.557 AC: 40283 AN: 72314

European-Finnish (FIN) AF: 0.408 AC: 20617 AN: 50488

Middle Eastern (MID) AF: 0.342 AC: 1830 AN: 5346

European-Non Finnish (NFE) AF: 0.334 AC: 351428 AN: 1053572

Other (OTH) AF: 0.369 AC: 20748 AN: 56300

GnomAD4 genome AF: 0.390 AC: 59181 AN: 151922 Hom.: 12097 Cov.: 32 AF XY: 0.396 AC XY: 29439 AN XY: 74266

African (AFR) AF: 0.420 AC: 17405 AN: 41430

American (AMR) AF: 0.454 AC: 6936 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 842 AN: 3468

East Asian (EAS) AF: 0.631 AC: 3246 AN: 5146

South Asian (SAS) AF: 0.572 AC: 2750 AN: 4810

European-Finnish (FIN) AF: 0.402 AC: 4241 AN: 10550

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22630 AN: 67932

Other (OTH) AF: 0.385 AC: 810 AN: 2104

Alfa AF: 0.349 Hom.: 9323

Bravo AF: 0.393

Asia WGS AF: 0.603 AC: 2098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.54
PhyloP100		0.075
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: rs13115988; hg19: chr4-90168882; COSMIC: COSV60884083;