rs7934888

Positions:

• chr11-123364998-T-G

Variant summary

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

The NM_001367421.2(GRAMD1B):​c.-85+6199T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 152,126 control chromosomes in the GnomAD database, including 14,849 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 0.36 (14849 hom., cov: 32)
• Consequence: GRAMD1B NM_001367421.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.397

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRAMD1B	NM_001367421.2	c.-85+6199T>G		intron_variant			NP_001354350.1
GRAMD1B	NM_001367420.2	c.26+6199T>G		intron_variant			NP_001354349.1
GRAMD1B	NM_001367419.2	c.26+6199T>G		intron_variant			NP_001354348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRAMD1B	ENST00000638157.1	c.-176+6199T>G		intron_variant		5		ENSP00000489896.1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54486 AN: 152008 Hom.: 14798 Cov.: 32

Gnomad AFR AF: 0.771

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.359 AC: 54591 AN: 152126 Hom.: 14849 Cov.: 32 AF XY: 0.351 AC XY: 26101 AN XY: 74400

Gnomad4 AFR AF: 0.771

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.316

Alfa AF: 0.229 Hom.: 6443

Bravo AF: 0.386

Asia WGS AF: 0.224 AC: 780 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.0
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7934888; hg19: chr11-123235706;