chr12-100748045-T-C

Position:

• chr12-100748045-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000644049.1(ANO4):​c.358+7940T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: ANO4 ENST00000644049.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301

Genes affected

ANO4 (HGNC:23837): (anoctamin 4) Enables intracellular calcium activated chloride channel activity. Involved in chloride transport. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO4	XM_011537911.3	c.451+7940T>C		intron_variant			XP_011536213.2
ANO4	XM_011537912.3	c.451+7940T>C		intron_variant			XP_011536214.2
ANO4	XM_011537913.3	c.451+7940T>C		intron_variant			XP_011536215.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO4	ENST00000644049.1	c.358+7940T>C		intron_variant				ENSP00000494481
ANO4	ENST00000549155.6	c.358+7940T>C		intron_variant, NMD_transcript_variant		2		ENSP00000449116

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.63
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17030538; hg19: chr12-101141823;