rs2741864

Variant names:

• chr11-3670891-G-A
• rs2741864
• NM_020402.4:c.61+361C>T

Variant summary

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

The NM_020402.4(CHRNA10):​c.61+361C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 152,042 control chromosomes in the GnomAD database, including 17,188 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 0.47 (17188 hom., cov: 32)
• Consequence: CHRNA10 NM_020402.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700
• Publications: 2 publications found

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]

NUP98 (HGNC:8068): (nucleoporin 98 and 96 precursor) Nuclear pore complexes (NPCs) regulate the transport of macromolecules between the nucleus and cytoplasm, and are composed of many polypeptide subunits, many of which belong to the nucleoporin family. This gene belongs to the nucleoporin gene family and encodes a 186 kDa precursor protein that undergoes autoproteolytic cleavage to generate a 98 kDa nucleoporin and 96 kDa nucleoporin. The 98 kDa nucleoporin contains a Gly-Leu-Phe-Gly (GLGF) repeat domain and participates in many cellular processes, including nuclear import, nuclear export, mitotic progression, and regulation of gene expression. The 96 kDa nucleoporin is a scaffold component of the NPC. Proteolytic cleavage is important for targeting of the proteins to the NPC. Translocations between this gene and many other partner genes have been observed in different leukemias. Rearrangements typically result in chimeras with the N-terminal GLGF domain of this gene to the C-terminus of the partner gene. Alternative splicing results in multiple transcript variants encoding different isoforms, at least two of which are proteolytically processed. Some variants lack the region that encodes the 96 kDa nucleoporin. [provided by RefSeq, Feb 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020402.4. 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
	CHRNA10	NM_020402.4	MANE Select	c.61+361C>T		intron	N/A	NP_065135.2
	CHRNA10	NM_001303034.2		c.-620+361C>T		intron	N/A	NP_001289963.1
	CHRNA10	NM_001303035.2		c.-553+361C>T		intron	N/A	NP_001289964.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA10	ENST00000250699.2	TSL:1 MANE Select	c.61+361C>T		intron	N/A	ENSP00000250699.2
	CHRNA10	ENST00000534359.1	TSL:1	c.-482+361C>T		intron	N/A	ENSP00000437107.1
	CHRNA10	ENST00000526599.1	TSL:1	n.61+361C>T		intron	N/A	ENSP00000432757.1

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71720 AN: 151924 Hom.: 17168 Cov.: 32

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.472 AC: 71791 AN: 152042 Hom.: 17188 Cov.: 32 AF XY: 0.473 AC XY: 35132 AN XY: 74302

African (AFR) AF: 0.431 AC: 17893 AN: 41476

American (AMR) AF: 0.639 AC: 9769 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1487 AN: 3472

East Asian (EAS) AF: 0.564 AC: 2905 AN: 5152

South Asian (SAS) AF: 0.410 AC: 1975 AN: 4818

European-Finnish (FIN) AF: 0.367 AC: 3875 AN: 10568

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32175 AN: 67960

Other (OTH) AF: 0.490 AC: 1035 AN: 2112

Alfa AF: 0.476 Hom.: 11195

Bravo AF: 0.496

Asia WGS AF: 0.497 AC: 1728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.2
DANN	Benign	0.35
PhyloP100		0.0070
PromoterAI		0.014	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2741864; hg19: chr11-3692121;