11-123557775-C-T

Variant names:

• chr11-123557775-C-T
• rs702738
• NM_001387025.1:c.453-19592C>T

Variant summary

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

The NM_001387025.1(GRAMD1B):​c.453-19592C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,014 control chromosomes in the GnomAD database, including 6,833 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 0.25 (6833 hom., cov: 32)
• Consequence: GRAMD1B NM_001387025.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.108
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRAMD1B	NM_001387025.1	c.453-19592C>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.453-19592C>T		intron_variant	Intron 2 of 19	5	NM_001387025.1	ENSP00000490062.1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38567 AN: 151896 Hom.: 6815 Cov.: 32

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0882

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.224

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.254 AC: 38642 AN: 152014 Hom.: 6833 Cov.: 32 AF XY: 0.247 AC XY: 18370 AN XY: 74318

African (AFR) AF: 0.499 AC: 20666 AN: 41428

American (AMR) AF: 0.252 AC: 3851 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 594 AN: 3468

East Asian (EAS) AF: 0.00290 AC: 15 AN: 5176

South Asian (SAS) AF: 0.117 AC: 563 AN: 4816

European-Finnish (FIN) AF: 0.0882 AC: 933 AN: 10582

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11265 AN: 67958

Other (OTH) AF: 0.226 AC: 476 AN: 2106

Alfa AF: 0.100 Hom.: 205

Bravo AF: 0.280

Asia WGS AF: 0.103 AC: 359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.5
DANN	Benign	0.57
PhyloP100		0.11
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: rs702738; hg19: chr11-123428483;