Genetic Variant CHRNA10:c.362+243T>A (chr11-3668953-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020402.4(CHRNA10):c.362+243T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 433,702 control chromosomes in the GnomAD database, including 94,570 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 0.62 ( 30255 hom., cov: 31)

Exomes 𝑓: 0.67 ( 64315 hom. )

Consequence

CHRNA10
NM_020402.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.05

Publications

3 publications found

Variant links:

Genes affected

CHRNA10 (HGNC:13800): (cholinergic receptor nicotinic alpha 10 subunit) Predicted to enable acetylcholine-gated cation-selective channel activity. Acts upstream of or within positive regulation of cytosolic calcium ion concentration. Predicted to be located in membrane. Predicted to be active in cholinergic synapse and neuron projection. Predicted to be integral component of postsynaptic specialization membrane. [provided by Alliance of Genome Resources, Apr 2022]

CHRNA10 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CHRNA10	NM_020402.4 link	c.362+243T>A	intron_variant	Intron 3 of 4	ENST00000250699.2	NP_065135.2	Q9GZZ6
CHRNA10	NM_001303034.2 link	c.-257+243T>A	intron_variant	Intron 3 of 4		NP_001289963.1	Q9GZZ6
CHRNA10	NM_001303035.2 link	c.-257+243T>A	intron_variant	Intron 3 of 4		NP_001289964.1	Q9GZZ6C4IXS7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHRNA10	ENST00000250699.2 link	c.362+243T>A	intron_variant	Intron 3 of 4	1	NM_020402.4	ENSP00000250699.2	Q9GZZ6
CHRNA10	ENST00000534359.1 link	c.-186+243T>A	intron_variant	Intron 3 of 4	1		ENSP00000437107.1	E9PNX2
CHRNA10	ENST00000526599.1 link	n.*133+243T>A	intron_variant	Intron 3 of 4	1		ENSP00000432757.1	E9PNT7
CHRNA10	ENST00000493827.2 link	n.552T>A	non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.621

AC:

94364

AN:

151884

Hom.:

30240

Cov.:

show subpopulations

Gnomad AFR

AF:

0.456

Gnomad AMI

AF:

0.673

Gnomad AMR

AF:

0.762

Gnomad ASJ

AF:

0.739

Gnomad EAS

AF:

0.686

Gnomad SAS

AF:

0.645

Gnomad FIN

AF:

0.585

Gnomad MID

AF:

0.680

Gnomad NFE

AF:

0.681

Gnomad OTH

AF:

0.643

GnomAD4 exome

AF:

0.671

AC:

189023

AN:

281700

Hom.:

64315

Cov.:

AF XY:

0.670

AC XY:

97413

AN XY:

145392

show subpopulations

African (AFR)

AF:

0.444

AC:

3787

AN:

8532

American (AMR)

AF:

0.801

AC:

8425

AN:

10516

Ashkenazi Jewish (ASJ)

AF:

0.733

AC:

6984

AN:

9534

East Asian (EAS)

AF:

0.677

AC:

13721

AN:

20274

South Asian (SAS)

AF:

0.622

AC:

13490

AN:

21686

European-Finnish (FIN)

AF:

0.615

AC:

11390

AN:

18530

Middle Eastern (MID)

AF:

0.659

AC:

898

AN:

1362

European-Non Finnish (NFE)

AF:

0.682

AC:

118537

AN:

173712

Other (OTH)

AF:

0.672

AC:

11791

AN:

17554

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

2835

5670

8506

11341

14176

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

562

1124

1686

2248

2810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.621

AC:

94425

AN:

152002

Hom.:

30255

Cov.:

AF XY:

0.621

AC XY:

46110

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.457

AC:

18909

AN:

41420

American (AMR)

AF:

0.763

AC:

11663

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.739

AC:

2564

AN:

3468

East Asian (EAS)

AF:

0.685

AC:

3532

AN:

5154

South Asian (SAS)

AF:

0.645

AC:

3105

AN:

4812

European-Finnish (FIN)

AF:

0.585

AC:

6186

AN:

10576

Middle Eastern (MID)

AF:

0.690

AC:

203

AN:

294

European-Non Finnish (NFE)

AF:

0.681

AC:

46299

AN:

67968

Other (OTH)

AF:

0.640

AC:

1350

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1726

3452

5177

6903

8629

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

772

1544

2316

3088

3860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.637

Hom.:

3918

Bravo

AF:

0.629

Asia WGS

AF:

0.663

AC:

2307

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.40

(source)

DANN

Benign

0.82

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over