chr11-123375446-G-A

Variant names:

• chr11-123375446-G-A
• rs10893032
• NM_001367421.2:c.-85+16647G>A

Variant summary

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

The NM_001367421.2(GRAMD1B):​c.-85+16647G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 151,912 control chromosomes in the GnomAD database, including 20,916 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 0.46 (20916 hom., cov: 31)
• Consequence: GRAMD1B NM_001367421.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRAMD1B	NM_001367421.2	c.-85+16647G>A		intron_variant	Intron 1 of 20		NP_001354350.1
GRAMD1B	NM_001367420.2	c.26+16647G>A		intron_variant	Intron 1 of 20		NP_001354349.1
GRAMD1B	NM_001367419.2	c.26+16647G>A		intron_variant	Intron 1 of 20		NP_001354348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRAMD1B	ENST00000638157.1	c.-176+16647G>A		intron_variant	Intron 1 of 20	5		ENSP00000489896.1

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69927 AN: 151794 Hom.: 20862 Cov.: 31

Gnomad AFR AF: 0.864

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.461 AC: 70023 AN: 151912 Hom.: 20916 Cov.: 31 AF XY: 0.451 AC XY: 33487 AN XY: 74224

African (AFR) AF: 0.864 AC: 35803 AN: 41434

American (AMR) AF: 0.346 AC: 5276 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1249 AN: 3466

East Asian (EAS) AF: 0.208 AC: 1074 AN: 5158

South Asian (SAS) AF: 0.251 AC: 1208 AN: 4814

European-Finnish (FIN) AF: 0.271 AC: 2852 AN: 10516

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21173 AN: 67940

Other (OTH) AF: 0.418 AC: 882 AN: 2108

Alfa AF: 0.383 Hom.: 23282

Bravo AF: 0.485

Asia WGS AF: 0.284 AC: 988 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.27
DANN	Benign	0.20
PhyloP100		-0.19

Splicing

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

Other links and lift over

dbSNP: rs10893032; hg19: chr11-123246154;