chr11-123598257-A-C

Variant names:

• chr11-123598257-A-C
• rs1709905
• NM_001387025.1:c.970-2211A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001387025.1(GRAMD1B):​c.970-2211A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: GRAMD1B NM_001387025.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 5 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]

SF3A3P2 (HGNC:23277): (splicing factor 3a, subunit 3 pseudogene 2)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRAMD1B	NM_001387025.1	MANE Select	c.970-2211A>C		intron	N/A	NP_001373954.1
	GRAMD1B	NM_001387024.1		c.970-2211A>C		intron	N/A	NP_001373953.1
	GRAMD1B	NM_001387026.1		c.967-2211A>C		intron	N/A	NP_001373955.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRAMD1B	ENST00000635736.2	TSL:5 MANE Select	c.970-2211A>C		intron	N/A	ENSP00000490062.1
	GRAMD1B	ENST00000529750.5	TSL:1	c.541-2211A>C		intron	N/A	ENSP00000436500.1
	GRAMD1B	ENST00000534764.1	TSL:1	c.529-2211A>C		intron	N/A	ENSP00000434214.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 24

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.2
DANN	Benign	0.60
PhyloP100		-1.0

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: rs1709905; hg19: chr11-123468965;