chr2-111618386-A-C

Variant names:

• chr2-111618386-A-C
• rs1448190
• ENST00000728313.1:n.715T>G

Variant summary

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

The ENST00000728313.1(ENSG00000295159):​n.715T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 152,106 control chromosomes in the GnomAD database, including 35,843 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 0.68 (35843 hom., cov: 33)
• Consequence: ENSG00000295159 ENST00000728313.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150
• Publications: 7 publications found

Genes affected

ENSG00000295159 (HGNC:):

ANAPC1 (HGNC:19988): (anaphase promoting complex subunit 1) This gene encodes a subunit of the anaphase-promoting complex. This complex is an E3 ubiquitin ligase that regulates progression through the metaphase to anaphase portion of the cell cycle by ubiquitinating proteins which targets them for degradation. [provided by RefSeq, Dec 2011]

ANAPC1 Gene-Disease associations (from GenCC):

• Rothmund-Thomson syndrome type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: ClinGen, Ambry Genetics, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000728313.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000295159	ENST00000728313.1		n.715T>G		non_coding_transcript_exon	Exon 2 of 2
	ENSG00000280878	ENST00000630717.1	TSL:5	n.27-18737A>C		intron	N/A
	ANAPC1	ENST00000643447.1		n.*140-3776T>G		intron	N/A	ENSP00000494863.1	A0A2R8YF63

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102862 AN: 151988 Hom.: 35820 Cov.: 33

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.800

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.666

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

GnomAD4 genome AF: 0.677 AC: 102933 AN: 152106 Hom.: 35843 Cov.: 33 AF XY: 0.675 AC XY: 50169 AN XY: 74356

African (AFR) AF: 0.577 AC: 23929 AN: 41462

American (AMR) AF: 0.684 AC: 10456 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 2567 AN: 3468

East Asian (EAS) AF: 0.254 AC: 1313 AN: 5170

South Asian (SAS) AF: 0.644 AC: 3109 AN: 4824

European-Finnish (FIN) AF: 0.800 AC: 8473 AN: 10588

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.748 AC: 50849 AN: 67998

Other (OTH) AF: 0.660 AC: 1393 AN: 2110

Alfa AF: 0.709 Hom.: 105865

Bravo AF: 0.663

Asia WGS AF: 0.462 AC: 1609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.5
DANN	Benign	0.77
PhyloP100		-0.015

Splicing

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

Other links and lift over

dbSNP: rs1448190; hg19: chr2-112375963;