11-123606644-G-A

Variant names:

• chr11-123606644-G-A
• rs2279519
• NM_001387025.1:c.1359G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001387025.1(GRAMD1B):​c.1359G>A​(p.Glu453Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 1,611,422 control chromosomes in the GnomAD database, including 81,245 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.28 (6062 hom., cov: 32)
  • Exomes 𝑓: 0.32 (75183 hom.)
• Consequence: GRAMD1B NM_001387025.1 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.755
• Publications: 16 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 11-123606644-G-A is Benign according to our data. Variant chr11-123606644-G-A is described in ClinVar as Benign. ClinVar VariationId is 3061028.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.755 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387025.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRAMD1B	NM_001387025.1	MANE Select	c.1359G>A	p.Glu453Glu	synonymous	Exon 11 of 20	NP_001373954.1	A0A1B0GUD6
	GRAMD1B	NM_001387024.1		c.1359G>A	p.Glu453Glu	synonymous	Exon 11 of 20	NP_001373953.1
	GRAMD1B	NM_001387026.1		c.1356G>A	p.Glu452Glu	synonymous	Exon 11 of 20	NP_001373955.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRAMD1B	ENST00000635736.2	TSL:5 MANE Select	c.1359G>A	p.Glu453Glu	synonymous	Exon 11 of 20	ENSP00000490062.1	A0A1B0GUD6
	GRAMD1B	ENST00000529750.5	TSL:1	c.930G>A	p.Glu310Glu	synonymous	Exon 10 of 20	ENSP00000436500.1	Q3KR37-1
	GRAMD1B	ENST00000534764.1	TSL:1	c.918G>A	p.Glu306Glu	synonymous	Exon 10 of 12	ENSP00000434214.1	E9PRD6

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42412 AN: 151978 Hom.: 6052 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.246

GnomAD2 exomes AF: 0.300 AC: 73615 AN: 245384 AF XY: 0.305

Gnomad AFR exome AF: 0.223

Gnomad AMR exome AF: 0.287

Gnomad ASJ exome AF: 0.278

Gnomad EAS exome AF: 0.161

Gnomad FIN exome AF: 0.281

Gnomad NFE exome AF: 0.316

Gnomad OTH exome AF: 0.274

GnomAD4 exome AF: 0.317 AC: 462774 AN: 1459326 Hom.: 75183 Cov.: 36 AF XY: 0.319 AC XY: 231811 AN XY: 725714

African (AFR) AF: 0.224 AC: 7509 AN: 33450

American (AMR) AF: 0.282 AC: 12507 AN: 44418

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 7291 AN: 26094

East Asian (EAS) AF: 0.233 AC: 9249 AN: 39626

South Asian (SAS) AF: 0.400 AC: 34259 AN: 85666

European-Finnish (FIN) AF: 0.285 AC: 15183 AN: 53256

Middle Eastern (MID) AF: 0.216 AC: 1244 AN: 5750

European-Non Finnish (NFE) AF: 0.321 AC: 356998 AN: 1110764

Other (OTH) AF: 0.307 AC: 18534 AN: 60302

GnomAD4 genome AF: 0.279 AC: 42462 AN: 152096 Hom.: 6062 Cov.: 32 AF XY: 0.278 AC XY: 20654 AN XY: 74350

African (AFR) AF: 0.226 AC: 9372 AN: 41500

American (AMR) AF: 0.252 AC: 3859 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 979 AN: 3470

East Asian (EAS) AF: 0.184 AC: 949 AN: 5170

South Asian (SAS) AF: 0.411 AC: 1980 AN: 4822

European-Finnish (FIN) AF: 0.269 AC: 2847 AN: 10572

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21628 AN: 67952

Other (OTH) AF: 0.253 AC: 534 AN: 2114

Alfa AF: 0.301 Hom.: 25595

Bravo AF: 0.273

Asia WGS AF: 0.328 AC: 1137 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	GRAMD1B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	5.0
DANN	Benign	0.53
PhyloP100		0.76
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2279519; hg19: chr11-123477352; COSMIC: COSV59204454; COSMIC: COSV59204454;