chr3-113866786-T-C

Variant names:

• chr3-113866786-T-C
• rs1025398
• NM_017577.5:c.175-2721T>C

Variant summary

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

The NM_017577.5(GRAMD1C):​c.175-2721T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 151,874 control chromosomes in the GnomAD database, including 8,794 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 0.33 (8794 hom., cov: 32)
• Consequence: GRAMD1C NM_017577.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214
• Publications: 12 publications found

Genes affected

GRAMD1C (HGNC:25252): (GRAM domain containing 1C) Predicted to enable cholesterol binding activity and cholesterol transfer activity. Predicted to be involved in cellular response to cholesterol. Predicted to be 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRAMD1C	NM_017577.5	c.175-2721T>C		intron_variant	Intron 2 of 17	ENST00000358160.9	NP_060047.3
GRAMD1C	XM_011512930.2	c.145-2721T>C		intron_variant	Intron 2 of 17		XP_011511232.1
GRAMD1C	XM_005247547.3	c.175-2721T>C		intron_variant	Intron 2 of 16		XP_005247604.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRAMD1C	ENST00000358160.9	c.175-2721T>C		intron_variant	Intron 2 of 17	1	NM_017577.5	ENSP00000350881.4

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50129 AN: 151758 Hom.: 8787 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.330 AC: 50161 AN: 151874 Hom.: 8794 Cov.: 32 AF XY: 0.332 AC XY: 24643 AN XY: 74222

African (AFR) AF: 0.236 AC: 9774 AN: 41444

American (AMR) AF: 0.380 AC: 5799 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1043 AN: 3470

East Asian (EAS) AF: 0.263 AC: 1358 AN: 5168

South Asian (SAS) AF: 0.243 AC: 1170 AN: 4820

European-Finnish (FIN) AF: 0.423 AC: 4422 AN: 10446

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.376 AC: 25534 AN: 67940

Other (OTH) AF: 0.315 AC: 665 AN: 2108

Alfa AF: 0.358 Hom.: 22303

Bravo AF: 0.324

Asia WGS AF: 0.275 AC: 957 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.66
PhyloP100		0.21
Mutation Taster		=100/0	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: rs1025398; hg19: chr3-113585633;