ENST00000943461.1:c.-452+14435A>G

Variant names:

• chr11-123373234-A-G
• rs11822822
• ENST00000943461.1:c.-452+14435A>G

Variant summary

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

The ENST00000943461.1(GRAMD1B):​c.-452+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 ENST00000943461.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000943461.1. 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_001367421.2		c.-85+14435A>G		intron	N/A	NP_001354350.1
	GRAMD1B	NM_001367420.2		c.26+14435A>G		intron	N/A	NP_001354349.1
	GRAMD1B	NM_001367419.2		c.26+14435A>G		intron	N/A	NP_001354348.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRAMD1B	ENST00000943461.1		c.-452+14435A>G		intron	N/A	ENSP00000613520.1
	GRAMD1B	ENST00000943462.1		c.-452+5772A>G		intron	N/A	ENSP00000613521.1
	GRAMD1B	ENST00000943463.1		c.-452+5884A>G		intron	N/A	ENSP00000613522.1

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

African (AFR) AF: 0.845 AC: 35053 AN: 41494

American (AMR) AF: 0.298 AC: 4564 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1114 AN: 3464

East Asian (EAS) AF: 0.141 AC: 728 AN: 5176

South Asian (SAS) AF: 0.199 AC: 958 AN: 4822

European-Finnish (FIN) AF: 0.152 AC: 1612 AN: 10610

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14057 AN: 67990

Other (OTH) AF: 0.356 AC: 753 AN: 2116

Alfa AF: 0.263 Hom.: 7222

Bravo AF: 0.422

Asia WGS AF: 0.234 AC: 814 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.8
DANN	Benign	0.79
PhyloP100		0.040

Splicing

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

Other links and lift over

dbSNP: rs11822822; hg19: chr11-123243942;