rs55998310

Variant names:

• chr4-40337233-T-C
• rs55998310
• NM_017581.4:c.234T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_017581.4(CHRNA9):​c.234T>C​(p.Thr78Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00754 in 1,614,194 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0059 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0077 (56 hom.)
• Consequence: CHRNA9 NM_017581.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.90
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 4-40337233-T-C is Benign according to our data. Variant chr4-40337233-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2654735.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00772 (11281/1461836) while in subpopulation MID AF = 0.018 (104/5768). AF 95% confidence interval is 0.0152. There are 56 homozygotes in GnomAdExome4. There are 5669 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017581.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA9	NM_017581.4	MANE Select	c.234T>C	p.Thr78Thr	synonymous	Exon 3 of 5	NP_060051.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA9	ENST00000310169.3	TSL:1 MANE Select	c.234T>C	p.Thr78Thr	synonymous	Exon 3 of 5	ENSP00000312663.2
	CHRNA9	ENST00000502377.1	TSL:3	n.-53T>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.00587 AC: 894 AN: 152240 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00471

Gnomad ASJ AF: 0.00807

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00641

Gnomad FIN AF: 0.00537

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00932

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00640 AC: 1608 AN: 251366 AF XY: 0.00647

Gnomad AFR exome AF: 0.00166

Gnomad AMR exome AF: 0.00431

Gnomad ASJ exome AF: 0.00903

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00684

Gnomad NFE exome AF: 0.00874

Gnomad OTH exome AF: 0.00766

GnomAD4 exome AF: 0.00772 AC: 11281 AN: 1461836 Hom.: 56 Cov.: 31 AF XY: 0.00780 AC XY: 5669 AN XY: 727214

African (AFR) AF: 0.00140 AC: 47 AN: 33478

American (AMR) AF: 0.00445 AC: 199 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00930 AC: 243 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00497 AC: 429 AN: 86252

European-Finnish (FIN) AF: 0.00711 AC: 380 AN: 53418

Middle Eastern (MID) AF: 0.0180 AC: 104 AN: 5768

European-Non Finnish (NFE) AF: 0.00844 AC: 9381 AN: 1111978

Other (OTH) AF: 0.00823 AC: 497 AN: 60392

GnomAD4 genome AF: 0.00586 AC: 893 AN: 152358 Hom.: 4 Cov.: 33 AF XY: 0.00573 AC XY: 427 AN XY: 74516

African (AFR) AF: 0.00144 AC: 60 AN: 41592

American (AMR) AF: 0.00470 AC: 72 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00807 AC: 28 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00642 AC: 31 AN: 4832

European-Finnish (FIN) AF: 0.00537 AC: 57 AN: 10622

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00932 AC: 634 AN: 68022

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.00746 Hom.: 4

Bravo AF: 0.00516

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.00943

EpiControl AF: 0.0102

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.13
DANN	Benign	0.38
PhyloP100		-3.9
Mutation Taster		=100/0	polymorphism

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: rs55998310; hg19: chr4-40339250;