chr11-123490689-G-A

Variant names:

• chr11-123490689-G-A
• rs735665
• NM_001387025.1:c.452+9796G>A

Variant summary

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

The NM_001387025.1(GRAMD1B):​c.452+9796G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,176 control chromosomes in the GnomAD database, including 2,171 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 0.15 (2171 hom., cov: 32)
• Consequence: GRAMD1B NM_001387025.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283
• Publications: 74 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.228 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRAMD1B	NM_001387025.1	MANE Select	c.452+9796G>A		intron	N/A	NP_001373954.1
	GRAMD1B	NM_001387024.1		c.452+9796G>A		intron	N/A	NP_001373953.1
	GRAMD1B	NM_001387026.1		c.449+9796G>A		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.452+9796G>A		intron	N/A	ENSP00000490062.1
	GRAMD1B	ENST00000638157.1	TSL:5	c.-98+9796G>A		intron	N/A	ENSP00000489896.1
	GRAMD1B	ENST00000633087.1	TSL:4	c.92+9796G>A		intron	N/A	ENSP00000488613.1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22618 AN: 152058 Hom.: 2171 Cov.: 32

Gnomad AFR AF: 0.0480

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.00597

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.149 AC: 22622 AN: 152176 Hom.: 2171 Cov.: 32 AF XY: 0.150 AC XY: 11126 AN XY: 74392

African (AFR) AF: 0.0479 AC: 1988 AN: 41546

American (AMR) AF: 0.234 AC: 3584 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 461 AN: 3470

East Asian (EAS) AF: 0.00599 AC: 31 AN: 5178

South Asian (SAS) AF: 0.129 AC: 622 AN: 4816

European-Finnish (FIN) AF: 0.220 AC: 2324 AN: 10584

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13170 AN: 67984

Other (OTH) AF: 0.152 AC: 320 AN: 2110

Alfa AF: 0.177 Hom.: 12564

Bravo AF: 0.147

Asia WGS AF: 0.0660 AC: 228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.81
DANN	Benign	0.70
PhyloP100		-0.28

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs735665; hg19: chr11-123361397;