ENST00000529750.5:c.-13C>T

Variant names:

• chr11-123526136-C-T
• rs17740690
• ENST00000529750.5:c.-13C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000529750.5(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 ENST00000529750.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.36
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000529750.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRAMD1B	NM_001387025.1	MANE Select	c.452+45243C>T		intron	N/A	NP_001373954.1
	GRAMD1B	NM_001387028.1		c.-13C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 20	NP_001373957.1
	GRAMD1B	NM_001286563.3		c.-13C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 21	NP_001273492.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRAMD1B	ENST00000529750.5	TSL:1	c.-13C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 20	ENSP00000436500.1
	GRAMD1B	ENST00000529750.5	TSL:1	c.-13C>T		5_prime_UTR	Exon 1 of 20	ENSP00000436500.1
	GRAMD1B	ENST00000635736.2	TSL:5 MANE Select	c.452+45243C>T		intron	N/A	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

GnomAD2 exomes AF: 0.0535 AC: 13177 AN: 246156 AF XY: 0.0545

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 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

African (AFR) AF: 0.00951 AC: 318 AN: 33454

American (AMR) AF: 0.0556 AC: 2483 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.0298 AC: 778 AN: 26104

East Asian (EAS) AF: 0.000756 AC: 30 AN: 39692

South Asian (SAS) AF: 0.0484 AC: 4160 AN: 85964

European-Finnish (FIN) AF: 0.0827 AC: 4414 AN: 53376

Middle Eastern (MID) AF: 0.0201 AC: 116 AN: 5766

European-Non Finnish (NFE) AF: 0.0705 AC: 78192 AN: 1108414

Other (OTH) AF: 0.0572 AC: 3446 AN: 60246

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

African (AFR) AF: 0.0127 AC: 529 AN: 41578

American (AMR) AF: 0.0530 AC: 810 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0239 AC: 83 AN: 3470

East Asian (EAS) AF: 0.00213 AC: 11 AN: 5172

South Asian (SAS) AF: 0.0431 AC: 208 AN: 4824

European-Finnish (FIN) AF: 0.0785 AC: 833 AN: 10610

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0724 AC: 4922 AN: 68030

Other (OTH) AF: 0.0364 AC: 77 AN: 2114

Alfa AF: 0.0621 Hom.: 598

Bravo AF: 0.0444

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	20
DANN	Benign	0.92
PhyloP100		2.4
PromoterAI		-0.088	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17740690; hg19: chr11-123396844;