19-48446029-G-T

Variant names:

• chr19-48446029-G-T
• rs1643487
• NM_031485.4:c.24G>T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_031485.4(GRWD1):​c.24G>T​(p.Arg8Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 1,591,636 control chromosomes in the GnomAD database, including 611,520 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 0.80 (50241 hom., cov: 31)
  • Exomes 𝑓: 0.88 (561279 hom.)
• Consequence: GRWD1 NM_031485.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.294

Genes affected

GRWD1 (HGNC:21270): (glutamate rich WD repeat containing 1) This gene encodes a glutamate-rich protein that contains five WD-repeat motifs. The encoded protein may play a critical role in ribosome biogenesis and may also play a role in histone methylation through interactions with CUL4-DDB1 ubiquitin E3 ligase. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP7: Synonymous conserved (PhyloP=0.294 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRWD1	NM_031485.4	c.24G>T	p.Arg8Arg	synonymous_variant	Exon 1 of 7	ENST00000253237.10	NP_113673.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRWD1	ENST00000253237.10	c.24G>T	p.Arg8Arg	synonymous_variant	Exon 1 of 7	1	NM_031485.4	ENSP00000253237.4
GRWD1	ENST00000598711.1	c.-123+115G>T		intron_variant	Intron 1 of 5	3		ENSP00000468943.1
GRWD1	ENST00000599949.1	n.38G>T		non_coding_transcript_exon_variant	Exon 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121654 AN: 151828 Hom.: 50220 Cov.: 31

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.948

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.939

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.787

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.908

Gnomad OTH AF: 0.817

GnomAD3 exomes AF: 0.835 AC: 177101 AN: 212062 Hom.: 75183 AF XY: 0.839 AC XY: 96530 AN XY: 115036

Gnomad AFR exome AF: 0.598

Gnomad AMR exome AF: 0.821

Gnomad ASJ exome AF: 0.938

Gnomad EAS exome AF: 0.597

Gnomad SAS exome AF: 0.783

Gnomad FIN exome AF: 0.878

Gnomad NFE exome AF: 0.907

Gnomad OTH exome AF: 0.870

GnomAD4 exome AF: 0.879 AC: 1265987 AN: 1439690 Hom.: 561279 Cov.: 66 AF XY: 0.878 AC XY: 626887 AN XY: 714212

Gnomad4 AFR exome AF: 0.592

Gnomad4 AMR exome AF: 0.826

Gnomad4 ASJ exome AF: 0.935

Gnomad4 EAS exome AF: 0.559

Gnomad4 SAS exome AF: 0.788

Gnomad4 FIN exome AF: 0.877

Gnomad4 NFE exome AF: 0.908

Gnomad4 OTH exome AF: 0.856

GnomAD4 genome AF: 0.801 AC: 121722 AN: 151946 Hom.: 50241 Cov.: 31 AF XY: 0.798 AC XY: 59292 AN XY: 74258

Gnomad4 AFR AF: 0.604

Gnomad4 AMR AF: 0.835

Gnomad4 ASJ AF: 0.939

Gnomad4 EAS AF: 0.594

Gnomad4 SAS AF: 0.788

Gnomad4 FIN AF: 0.881

Gnomad4 NFE AF: 0.908

Gnomad4 OTH AF: 0.818

Alfa AF: 0.893 Hom.: 41817

Bravo AF: 0.790

Asia WGS AF: 0.685 AC: 2384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.6
DANN	Benign	0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7

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: rs1643487; hg19: chr19-48949286; COSMIC: COSV53517496; COSMIC: COSV53517496;