chr11-419906-C-T

Position:

• chr11-419906-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001012302.3(ANO9):​c.1787-177G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 1,427,516 control chromosomes in the GnomAD database, including 470,779 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 0.81 (49244 hom., cov: 32)
  • Exomes 𝑓: 0.81 (421535 hom.)
• Consequence: ANO9 NM_001012302.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.257

Genes affected

ANO9 (HGNC:20679): (anoctamin 9) The protein encoded by this gene is a member of the TMEM16 (anoctamin) family of proteins, some of which form integral membrane calcium-activated chloride channels. The function of the encoded protein has yet to be elucidated, although it may have channel-forming abilities and also may have phospholipid scramblase activity. This gene has been observed to be upregulated in stage II and III colorectal cancers. [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO9	NM_001012302.3	c.1787-177G>A		intron_variant		ENST00000332826.7	NP_001012302.2
ANO9	NM_001347882.2	c.1355-177G>A		intron_variant			NP_001334811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO9	ENST00000332826.7	c.1787-177G>A		intron_variant		1	NM_001012302.3	ENSP00000332788	P1

Frequencies

GnomAD3 genomes AF: 0.812 AC: 122008 AN: 150242 Hom.: 49214 Cov.: 32

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.860

Gnomad AMR AF: 0.793

Gnomad ASJ AF: 0.853

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.962

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.901

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.822

GnomAD4 exome AF: 0.811 AC: 1036365 AN: 1277164 Hom.: 421535 Cov.: 45 AF XY: 0.815 AC XY: 504851 AN XY: 619204

Gnomad4 AFR exome AF: 0.788

Gnomad4 AMR exome AF: 0.767

Gnomad4 ASJ exome AF: 0.846

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.958

Gnomad4 FIN exome AF: 0.792

Gnomad4 NFE exome AF: 0.796

Gnomad4 OTH exome AF: 0.840

GnomAD4 genome AF: 0.812 AC: 122088 AN: 150352 Hom.: 49244 Cov.: 32 AF XY: 0.817 AC XY: 59989 AN XY: 73454

Gnomad4 AFR AF: 0.796

Gnomad4 AMR AF: 0.793

Gnomad4 ASJ AF: 0.853

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.962

Gnomad4 FIN AF: 0.806

Gnomad4 NFE AF: 0.798

Gnomad4 OTH AF: 0.824

Alfa AF: 0.795 Hom.: 25009

Bravo AF: 0.798

Asia WGS AF: 0.957 AC: 3327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.53
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7484182; hg19: chr11-419906;