11-123603823-T-C

Position:

• chr11-123603823-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001387025.1(GRAMD1B):​c.1166+282T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 152,040 control chromosomes in the GnomAD database, including 19,272 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 0.50 (19272 hom., cov: 33)
• Consequence: GRAMD1B NM_001387025.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRAMD1B	NM_001387025.1	c.1166+282T>C		intron_variant		ENST00000635736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRAMD1B	ENST00000635736.2	c.1166+282T>C		intron_variant		5	NM_001387025.1	P1

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76187 AN: 151922 Hom.: 19251 Cov.: 33

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.502 AC: 76257 AN: 152040 Hom.: 19272 Cov.: 33 AF XY: 0.500 AC XY: 37196 AN XY: 74322

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.514

Gnomad4 ASJ AF: 0.446

Gnomad4 EAS AF: 0.423

Gnomad4 SAS AF: 0.554

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.469

Alfa AF: 0.488 Hom.: 17818

Bravo AF: 0.507

Asia WGS AF: 0.514 AC: 1785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	12
DANN	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs1274214; hg19: chr11-123474531;