11-123603823-T-C

Variant names:

• chr11-123603823-T-C
• rs1274214
• NM_001387025.1:c.1166+282T>C

Variant summary

Our verdict is Benign. The variant received -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
• 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387025.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRAMD1B	NM_001387025.1	MANE Select	c.1166+282T>C		intron	N/A	NP_001373954.1	A0A1B0GUD6
	GRAMD1B	NM_001387024.1		c.1166+282T>C		intron	N/A	NP_001373953.1
	GRAMD1B	NM_001387026.1		c.1163+282T>C		intron	N/A	NP_001373955.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRAMD1B	ENST00000635736.2	TSL:5 MANE Select	c.1166+282T>C		intron	N/A	ENSP00000490062.1	A0A1B0GUD6
	GRAMD1B	ENST00000529750.5	TSL:1	c.737+282T>C		intron	N/A	ENSP00000436500.1	Q3KR37-1
	GRAMD1B	ENST00000534764.1	TSL:1	c.725+282T>C		intron	N/A	ENSP00000434214.1	E9PRD6

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

African (AFR) AF: 0.537 AC: 22255 AN: 41438

American (AMR) AF: 0.514 AC: 7852 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1547 AN: 3468

East Asian (EAS) AF: 0.423 AC: 2187 AN: 5168

South Asian (SAS) AF: 0.554 AC: 2671 AN: 4824

European-Finnish (FIN) AF: 0.460 AC: 4863 AN: 10562

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.490 AC: 33283 AN: 67980

Other (OTH) AF: 0.469 AC: 990 AN: 2112

Alfa AF: 0.491 Hom.: 23511

Bravo AF: 0.507

Asia WGS AF: 0.514 AC: 1785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	12
DANN	Benign	0.39
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1274214; hg19: chr11-123474531;