11-123364998-T-G

Variant names:

• chr11-123364998-T-G
• rs7934888
• NM_001367421.2:c.-85+6199T>G

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+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
• Publications: 1 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=-0.82).
• 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 rank	MANE	Protein	UniProt
GRAMD1B	NM_001367421.2	c.-85+6199T>G		intron_variant	Intron 1 of 20		NP_001354350.1
GRAMD1B	NM_001367420.2	c.26+6199T>G		intron_variant	Intron 1 of 20		NP_001354349.1
GRAMD1B	NM_001367419.2	c.26+6199T>G		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+6199T>G		intron_variant	Intron 1 of 20	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

African (AFR) AF: 0.771 AC: 31974 AN: 41450

American (AMR) AF: 0.260 AC: 3968 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 998 AN: 3468

East Asian (EAS) AF: 0.142 AC: 736 AN: 5192

South Asian (SAS) AF: 0.196 AC: 946 AN: 4822

European-Finnish (FIN) AF: 0.150 AC: 1589 AN: 10594

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13337 AN: 67998

Other (OTH) AF: 0.316 AC: 667 AN: 2112

Alfa AF: 0.248 Hom.: 10268

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
PhyloP100		0.40

Splicing

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

Other links and lift over

dbSNP: rs7934888; hg19: chr11-123235706;