NM_001387025.1:c.452+38624C>T

Variant names:

• chr11-123519517-C-T
• rs12799226
• NM_001387025.1:c.452+38624C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4 BA1

The NM_001387025.1(GRAMD1B):​c.452+38624C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,204 control chromosomes in the GnomAD database, including 2,906 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 0.19 (2906 hom., cov: 33)
• Consequence: GRAMD1B NM_001387025.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46
• Publications: 10 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.18).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRAMD1B	NM_001387025.1	c.452+38624C>T		intron_variant	Intron 2 of 19	ENST00000635736.2	NP_001373954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRAMD1B	ENST00000635736.2	c.452+38624C>T		intron_variant	Intron 2 of 19	5	NM_001387025.1	ENSP00000490062.1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28196 AN: 152086 Hom.: 2904 Cov.: 33

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.00789

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.185 AC: 28208 AN: 152204 Hom.: 2906 Cov.: 33 AF XY: 0.186 AC XY: 13814 AN XY: 74416

African (AFR) AF: 0.134 AC: 5554 AN: 41540

American (AMR) AF: 0.257 AC: 3935 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 698 AN: 3470

East Asian (EAS) AF: 0.00791 AC: 41 AN: 5182

South Asian (SAS) AF: 0.157 AC: 755 AN: 4824

European-Finnish (FIN) AF: 0.237 AC: 2511 AN: 10590

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14182 AN: 67984

Other (OTH) AF: 0.187 AC: 395 AN: 2114

Alfa AF: 0.201 Hom.: 13548

Bravo AF: 0.185

Asia WGS AF: 0.0850 AC: 295 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.18
CADD	Benign	20
DANN	Benign	0.80
PhyloP100		2.5

Splicing

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

Other links and lift over

dbSNP: rs12799226; hg19: chr11-123390225;