rs17740690

Variant names:

• chr11-123526136-C-T
• rs17740690
• ENST00000529750:c.-13C>T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001387028.1(GRAMD1B):​c.-13C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.063 in 1,609,970 control chromosomes in the GnomAD database, including 3,680 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 0.050 (239 hom., cov: 32)
  • Exomes 𝑓: 0.064 (3441 hom.)
• Consequence: GRAMD1B NM_001387028.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.36

Genes affected

GRAMD1B (HGNC:29214): (GRAM domain containing 1B) Predicted to enable cholesterol binding activity; cholesterol transfer activity; and phospholipid binding activity. Predicted to be involved in cellular response to cholesterol and cholesterol homeostasis. Located in endoplasmic reticulum membrane; endoplasmic reticulum-plasma membrane contact site; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRAMD1B	NM_001387025.1	c.452+45243C>T		intron_variant	Intron 2 of 19	ENST00000635736.2	NP_001373954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRAMD1B	ENST00000635736.2	c.452+45243C>T		intron_variant	Intron 2 of 19	5	NM_001387025.1	ENSP00000490062.1

Frequencies

GnomAD3 genomes AF: 0.0496 AC: 7549 AN: 152180 Hom.: 239 Cov.: 32

Gnomad AFR AF: 0.0128

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0532

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0431

Gnomad FIN AF: 0.0785

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0724

Gnomad OTH AF: 0.0368

GnomAD3 exomes AF: 0.0535 AC: 13177 AN: 246156 Hom.: 430 AF XY: 0.0545 AC XY: 7293 AN XY: 133694

Gnomad AFR exome AF: 0.0118

Gnomad AMR exome AF: 0.0551

Gnomad ASJ exome AF: 0.0283

Gnomad EAS exome AF: 0.000669

Gnomad SAS exome AF: 0.0480

Gnomad FIN exome AF: 0.0807

Gnomad NFE exome AF: 0.0659

Gnomad OTH exome AF: 0.0553

GnomAD4 exome AF: 0.0644 AC: 93937 AN: 1457672 Hom.: 3441 Cov.: 29 AF XY: 0.0641 AC XY: 46525 AN XY: 725258

Gnomad4 AFR exome AF: 0.00951

Gnomad4 AMR exome AF: 0.0556

Gnomad4 ASJ exome AF: 0.0298

Gnomad4 EAS exome AF: 0.000756

Gnomad4 SAS exome AF: 0.0484

Gnomad4 FIN exome AF: 0.0827

Gnomad4 NFE exome AF: 0.0705

Gnomad4 OTH exome AF: 0.0572

GnomAD4 genome AF: 0.0495 AC: 7542 AN: 152298 Hom.: 239 Cov.: 32 AF XY: 0.0490 AC XY: 3652 AN XY: 74456

Gnomad4 AFR AF: 0.0127

Gnomad4 AMR AF: 0.0530

Gnomad4 ASJ AF: 0.0239

Gnomad4 EAS AF: 0.00213

Gnomad4 SAS AF: 0.0431

Gnomad4 FIN AF: 0.0785

Gnomad4 NFE AF: 0.0724

Gnomad4 OTH AF: 0.0364

Alfa AF: 0.0633 Hom.: 465

Bravo AF: 0.0444

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	20
DANN	Benign	0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs17740690; hg19: chr11-123396844;