16-309953-A-G

Variant names:

• chr16-309953-A-G
• rs2301522
• NM_003502.4:c.1116+20T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_003502.4(AXIN1):​c.1116+20T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 1,610,148 control chromosomes in the GnomAD database, including 351,474 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.69 (38021 hom., cov: 34)
  • Exomes 𝑓: 0.65 (313453 hom.)
• Consequence: AXIN1 NM_003502.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135

Genes affected

AXIN1 (HGNC:903): (axin 1) This gene encodes a cytoplasmic protein which contains a regulation of G-protein signaling (RGS) domain and a dishevelled and axin (DIX) domain. The encoded protein interacts with adenomatosis polyposis coli, catenin beta-1, glycogen synthase kinase 3 beta, protein phosphate 2, and itself. This protein functions as a negative regulator of the wingless-type MMTV integration site family, member 1 (WNT) signaling pathway and can induce apoptosis. The crystal structure of a portion of this protein, alone and in a complex with other proteins, has been resolved. Mutations in this gene have been associated with hepatocellular carcinoma, hepatoblastomas, ovarian endometriod adenocarcinomas, and medullablastomas. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 16-309953-A-G is Benign according to our data. Variant chr16-309953-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AXIN1	NM_003502.4	c.1116+20T>C		intron_variant	Intron 4 of 10	ENST00000262320.8	NP_003493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AXIN1	ENST00000262320.8	c.1116+20T>C		intron_variant	Intron 4 of 10	1	NM_003502.4	ENSP00000262320.3
AXIN1	ENST00000354866.7	c.1116+20T>C		intron_variant	Intron 4 of 9	1		ENSP00000346935.3
AXIN1	ENST00000461023.5	n.413+20T>C		intron_variant	Intron 3 of 7	2
AXIN1	ENST00000481769.1	n.543+20T>C		intron_variant	Intron 3 of 4	3

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105592 AN: 152066 Hom.: 37957 Cov.: 34

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.637

GnomAD2 exomes AF: 0.624 AC: 153221 AN: 245694 AF XY: 0.630

Gnomad AFR exome AF: 0.890

Gnomad AMR exome AF: 0.518

Gnomad ASJ exome AF: 0.515

Gnomad EAS exome AF: 0.332

Gnomad FIN exome AF: 0.632

Gnomad NFE exome AF: 0.647

Gnomad OTH exome AF: 0.611

GnomAD4 exome AF: 0.652 AC: 950037 AN: 1457964 Hom.: 313453 Cov.: 34 AF XY: 0.653 AC XY: 473869 AN XY: 725326

African (AFR) AF: 0.889 AC: 29732 AN: 33434

American (AMR) AF: 0.523 AC: 23286 AN: 44544

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 13544 AN: 26112

East Asian (EAS) AF: 0.366 AC: 14512 AN: 39636

South Asian (SAS) AF: 0.728 AC: 62615 AN: 86042

European-Finnish (FIN) AF: 0.633 AC: 33245 AN: 52502

Middle Eastern (MID) AF: 0.564 AC: 3152 AN: 5590

European-Non Finnish (NFE) AF: 0.659 AC: 731709 AN: 1109860

Other (OTH) AF: 0.635 AC: 38242 AN: 60244

GnomAD4 genome AF: 0.695 AC: 105713 AN: 152184 Hom.: 38021 Cov.: 34 AF XY: 0.692 AC XY: 51509 AN XY: 74390

African (AFR) AF: 0.877 AC: 36434 AN: 41554

American (AMR) AF: 0.591 AC: 9038 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 1775 AN: 3472

East Asian (EAS) AF: 0.351 AC: 1815 AN: 5164

South Asian (SAS) AF: 0.737 AC: 3557 AN: 4824

European-Finnish (FIN) AF: 0.643 AC: 6812 AN: 10588

Middle Eastern (MID) AF: 0.551 AC: 161 AN: 292

European-Non Finnish (NFE) AF: 0.650 AC: 44157 AN: 67982

Other (OTH) AF: 0.639 AC: 1353 AN: 2116

Alfa AF: 0.662 Hom.: 24494

Bravo AF: 0.691

Asia WGS AF: 0.592 AC: 2055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.3
DANN	Benign	0.37
PhyloP100		-0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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

Publications

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Other links and lift over

dbSNP: rs2301522; hg19: chr16-359953; COSMIC: COSV51992204;