rs11822822

Positions:

• chr11-123373234-A-G
• chr11-123373234-A-T

Variant summary

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

The NM_001367421.2(GRAMD1B):​c.-85+14435A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 152,172 control chromosomes in the GnomAD database, including 17,753 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 0.39 (17753 hom., cov: 32)
• Consequence: GRAMD1B NM_001367421.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRAMD1B	NM_001367418.2	c.26+14435A>G		intron_variant
GRAMD1B	NM_001367419.2	c.26+14435A>G		intron_variant
GRAMD1B	NM_001367420.2	c.26+14435A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRAMD1B	ENST00000638157.1	c.-176+14435A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59129 AN: 152054 Hom.: 17696 Cov.: 32

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.389 AC: 59237 AN: 152172 Hom.: 17753 Cov.: 32 AF XY: 0.380 AC XY: 28259 AN XY: 74398

Gnomad4 AFR AF: 0.845

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.356

Alfa AF: 0.250 Hom.: 4534

Bravo AF: 0.422

Asia WGS AF: 0.234 AC: 814 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.8
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11822822; hg19: chr11-123243942;