rs735665

chr11-123490689-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRAMD1B	NM_001387025.1	c.452+9796G>A		intron_variant		ENST00000635736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRAMD1B	ENST00000635736.2	c.452+9796G>A		intron_variant		5	NM_001387025.1	P1
GRAMD1B	ENST00000633087.1	c.92+9796G>A		intron_variant		4
GRAMD1B	ENST00000633646.1	c.-98+9796G>A		intron_variant		3
GRAMD1B	ENST00000638157.1	c.-98+9796G>A		intron_variant		5

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

Gnomad4 AFR AF: 0.0479

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.00599

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.152

Alfa AF: 0.180 Hom.: 6090

Bravo AF: 0.147

Asia WGS AF: 0.0660 AC: 228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.81
Dann	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs735665; hg19: chr11-123361397;