2-230868988-T-C

Variant names:

• chr2-230868988-T-C
• rs3111754
• NM_030926.6:c.120+3843T>C

Variant summary

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

The NM_030926.6(ITM2C):​c.120+3843T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 152,176 control chromosomes in the GnomAD database, including 16,649 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 0.44 (16649 hom., cov: 33)
• Consequence: ITM2C NM_030926.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.66
• Publications: 9 publications found

Genes affected

ITM2C (HGNC:6175): (integral membrane protein 2C) Enables amyloid-beta binding activity. Involved in negative regulation of neuron projection development and neuron differentiation. Located in several cellular components, including Golgi apparatus; lysosome; and perinuclear region of cytoplasm. [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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030926.6. 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
	ITM2C	NM_030926.6	MANE Select	c.120+3843T>C		intron	N/A	NP_112188.1	Q9NQX7-1
	ITM2C	NM_001287241.2		c.120+3843T>C		intron	N/A	NP_001274170.1	Q9NQX7-1
	ITM2C	NM_001012516.2		c.120+3843T>C		intron	N/A	NP_001012534.1	Q9NQX7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITM2C	ENST00000326427.11	TSL:1 MANE Select	c.120+3843T>C		intron	N/A	ENSP00000322730.6	Q9NQX7-1
	ITM2C	ENST00000326407.10	TSL:1	c.120+3843T>C		intron	N/A	ENSP00000322100.6	Q9NQX7-3
	ITM2C	ENST00000335005.10	TSL:1	c.120+3843T>C		intron	N/A	ENSP00000335121.6	Q9NQX7-2

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67605 AN: 152058 Hom.: 16633 Cov.: 33

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.650

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.445 AC: 67668 AN: 152176 Hom.: 16649 Cov.: 33 AF XY: 0.455 AC XY: 33859 AN XY: 74386

African (AFR) AF: 0.251 AC: 10430 AN: 41524

American (AMR) AF: 0.585 AC: 8946 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 1829 AN: 3468

East Asian (EAS) AF: 0.841 AC: 4355 AN: 5178

South Asian (SAS) AF: 0.563 AC: 2718 AN: 4824

European-Finnish (FIN) AF: 0.538 AC: 5686 AN: 10576

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.470 AC: 31977 AN: 68000

Other (OTH) AF: 0.474 AC: 1001 AN: 2110

Alfa AF: 0.472 Hom.: 9216

Bravo AF: 0.443

Asia WGS AF: 0.691 AC: 2401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.5
DANN	Benign	0.83
PhyloP100		2.7
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3111754;

hg19: chr2-231733703;