rs7304749

Variant names:

• chr12-45296318-C-T
• rs7304749
• NM_001025356.3:c.71-5696C>T

Variant summary

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

The NM_001025356.3(ANO6):​c.71-5696C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.908 in 152,146 control chromosomes in the GnomAD database, including 63,530 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 0.91 (63530 hom., cov: 31)
• Consequence: ANO6 NM_001025356.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149
• Publications: 1 publications found

Genes affected

ANO6 (HGNC:25240): (anoctamin 6) This gene encodes a multi-pass transmembrane protein that belongs to the anoctamin family. This protein is an essential component for the calcium-dependent exposure of phosphatidylserine on the cell surface. The scrambling of phospholipid occurs in various biological systems, such as when blood platelets are activated, they expose phosphatidylserine to trigger the clotting system. Mutations in this gene are associated with Scott syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2011]

ANO6 Gene-Disease associations (from GenCC):

• Scott syndrome

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

ENSG00000293678 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO6	NM_001025356.3	c.71-5696C>T		intron_variant	Intron 1 of 19	ENST00000320560.13	NP_001020527.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO6	ENST00000320560.13	c.71-5696C>T		intron_variant	Intron 1 of 19	1	NM_001025356.3	ENSP00000320087.8

Frequencies

GnomAD3 genomes AF: 0.908 AC: 138013 AN: 152028 Hom.: 63507 Cov.: 31

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.929

Gnomad ASJ AF: 0.971

Gnomad EAS AF: 0.915

Gnomad SAS AF: 0.930

Gnomad FIN AF: 0.972

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.987

Gnomad OTH AF: 0.924

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

GnomAD4 genome AF: 0.908 AC: 138085 AN: 152146 Hom.: 63530 Cov.: 31 AF XY: 0.907 AC XY: 67486 AN XY: 74382

African (AFR) AF: 0.740 AC: 30666 AN: 41440

American (AMR) AF: 0.929 AC: 14196 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.971 AC: 3372 AN: 3472

East Asian (EAS) AF: 0.915 AC: 4731 AN: 5170

South Asian (SAS) AF: 0.930 AC: 4482 AN: 4820

European-Finnish (FIN) AF: 0.972 AC: 10311 AN: 10610

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.987 AC: 67175 AN: 68032

Other (OTH) AF: 0.925 AC: 1952 AN: 2110

Alfa AF: 0.933 Hom.: 10896

Bravo AF: 0.898

Asia WGS AF: 0.914 AC: 3178 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	1.2
DANN	Benign	0.31
PhyloP100		-0.15
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: rs7304749; hg19: chr12-45690101;