rs9653414

Variant names:

• chr2-111877160-G-A
• rs9653414
• NM_022662.4:c.375+1650C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_022662.4(ANAPC1):​c.375+1650C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 143,770 control chromosomes in the GnomAD database, including 24,285 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 0.57 (24285 hom., cov: 23)
• Consequence: ANAPC1 NM_022662.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215
• Publications: 5 publications found

Genes affected

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: Orphanet, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BS2: High Homozygotes in GnomAd4 at 24285 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANAPC1	NM_022662.4	c.375+1650C>T		intron_variant	Intron 3 of 47	ENST00000341068.8	NP_073153.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANAPC1	ENST00000341068.8	c.375+1650C>T		intron_variant	Intron 3 of 47	1	NM_022662.4	ENSP00000339109.3
ANAPC1	ENST00000628342.1	c.375+1650C>T		intron_variant	Intron 2 of 3	5		ENSP00000486322.1
ANAPC1	ENST00000451367.3	n.375+1650C>T		intron_variant	Intron 2 of 4	5		ENSP00000405375.1
ANAPC1	ENST00000489177.1	n.1148+1650C>T		intron_variant	Intron 3 of 4	5

Frequencies

GnomAD3 genomes AF: 0.567 AC: 81402 AN: 143652 Hom.: 24259 Cov.: 23

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.663

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.575

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

GnomAD4 genome AF: 0.567 AC: 81489 AN: 143770 Hom.: 24285 Cov.: 23 AF XY: 0.569 AC XY: 39591 AN XY: 69638

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.382 AC: 15034 AN: 39394

American (AMR) AF: 0.614 AC: 8548 AN: 13930

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1872 AN: 3374

East Asian (EAS) AF: 0.558 AC: 2740 AN: 4908

South Asian (SAS) AF: 0.672 AC: 2917 AN: 4342

European-Finnish (FIN) AF: 0.631 AC: 5947 AN: 9426

Middle Eastern (MID) AF: 0.669 AC: 194 AN: 290

European-Non Finnish (NFE) AF: 0.651 AC: 42520 AN: 65322

Other (OTH) AF: 0.576 AC: 1110 AN: 1926

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.637 Hom.: 48588

Bravo AF: 0.566

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.53
DANN	Benign	0.63
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: rs9653414; hg19: chr2-112634737;