11-123550694-A-G

Variant names:

• chr11-123550694-A-G
• rs1029278
• NM_001387025.1:c.453-26673A>G

Variant summary

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

The NM_001387024.1(GRAMD1B):​c.453-26673A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 152,072 control chromosomes in the GnomAD database, including 41,843 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 0.73 (41843 hom., cov: 31)
• Consequence: GRAMD1B NM_001387024.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.707
• Publications: 2 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387024.1. 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.453-26673A>G		intron	N/A	NP_001373954.1
	GRAMD1B	NM_001387024.1		c.453-26673A>G		intron	N/A	NP_001373953.1
	GRAMD1B	NM_001387026.1		c.450-26673A>G		intron	N/A	NP_001373955.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRAMD1B	ENST00000635736.2	TSL:5 MANE Select	c.453-26673A>G		intron	N/A	ENSP00000490062.1
	GRAMD1B	ENST00000529750.5	TSL:1	c.23+24523A>G		intron	N/A	ENSP00000436500.1
	GRAMD1B	ENST00000943465.1		c.453-26673A>G		intron	N/A	ENSP00000613524.1

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111644 AN: 151954 Hom.: 41785 Cov.: 31

Gnomad AFR AF: 0.879

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.760

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.731

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

GnomAD4 genome AF: 0.735 AC: 111768 AN: 152072 Hom.: 41843 Cov.: 31 AF XY: 0.736 AC XY: 54730 AN XY: 74318

African (AFR) AF: 0.879 AC: 36497 AN: 41512

American (AMR) AF: 0.760 AC: 11611 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2265 AN: 3472

East Asian (EAS) AF: 0.681 AC: 3507 AN: 5146

South Asian (SAS) AF: 0.516 AC: 2484 AN: 4812

European-Finnish (FIN) AF: 0.735 AC: 7761 AN: 10564

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.666 AC: 45302 AN: 67972

Other (OTH) AF: 0.733 AC: 1549 AN: 2112

Alfa AF: 0.692 Hom.: 63080

Bravo AF: 0.747

Asia WGS AF: 0.598 AC: 2079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.9
DANN	Benign	0.58
PhyloP100		-0.71
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1029278; hg19: chr11-123421402;