rs56299220

Positions:

• chr4-40335989-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_017581.4(CHRNA9):​c.210+17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00299 in 1,603,116 control chromosomes in the GnomAD database, including 15 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 0.0017 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (14 hom.)
• Consequence: CHRNA9 NM_017581.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.976

Genes affected

CHRNA9 (HGNC:14079): (cholinergic receptor nicotinic alpha 9 subunit) This gene is a member of the ligand-gated ionic channel family and nicotinic acetylcholine receptor gene superfamily. It encodes a plasma membrane protein that forms homo- or hetero-oligomeric divalent cation channels. This protein is involved in cochlea hair cell development and is also expressed in the outer hair cells (OHCs) of the adult cochlea. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BS2: High Homozygotes in GnomAdExome4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA9	NM_017581.4	c.210+17G>A		intron_variant		ENST00000310169.3	NP_060051.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA9	ENST00000310169.3	c.210+17G>A		intron_variant		1	NM_017581.4	ENSP00000312663	P1

Frequencies

GnomAD3 genomes AF: 0.00173 AC: 263 AN: 152184 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000676

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00317

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00170 AC: 421 AN: 248168 Hom.: 0 AF XY: 0.00172 AC XY: 231 AN XY: 134060

Gnomad AFR exome AF: 0.000493

Gnomad AMR exome AF: 0.000560

Gnomad ASJ exome AF: 0.000504

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000734

Gnomad FIN exome AF: 0.000420

Gnomad NFE exome AF: 0.00313

Gnomad OTH exome AF: 0.000995

GnomAD4 exome AF: 0.00313 AC: 4537 AN: 1450814 Hom.: 14 Cov.: 27 AF XY: 0.00301 AC XY: 2172 AN XY: 722098

Gnomad4 AFR exome AF: 0.000451

Gnomad4 AMR exome AF: 0.000520

Gnomad4 ASJ exome AF: 0.000654

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000608

Gnomad4 FIN exome AF: 0.000545

Gnomad4 NFE exome AF: 0.00389

Gnomad4 OTH exome AF: 0.00160

GnomAD4 genome AF: 0.00173 AC: 263 AN: 152302 Hom.: 1 Cov.: 32 AF XY: 0.00124 AC XY: 92 AN XY: 74470

Gnomad4 AFR AF: 0.000674

Gnomad4 AMR AF: 0.000458

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00318

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00222 Hom.: 0

Bravo AF: 0.00162

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.5
DANN	Benign	0.61

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

LitVar

Other links and lift over

dbSNP: rs56299220; hg19: chr4-40338006;