rs1830756

Variant names:

• chr13-107427875-C-A
• rs1830756
• NM_001080396.3:c.916-217120G>T

Variant summary

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

The NM_001080396.3(NALF1):​c.916-217120G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,068 control chromosomes in the GnomAD database, including 4,715 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 0.24 (4715 hom., cov: 32)
• Consequence: NALF1 NM_001080396.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338
• Publications: 5 publications found

Genes affected

NALF1 (HGNC:33877): (NALCN channel auxiliary factor 1) Predicted to contribute to stretch-activated, cation-selective, calcium channel activity. Predicted to be involved in calcium ion import across plasma membrane. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NALF1	NM_001080396.3	c.916-217120G>T		intron_variant	Intron 1 of 2	ENST00000375915.4	NP_001073865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NALF1	ENST00000375915.4	c.916-217120G>T		intron_variant	Intron 1 of 2	1	NM_001080396.3	ENSP00000365080.1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36834 AN: 151950 Hom.: 4718 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.242 AC: 36828 AN: 152068 Hom.: 4715 Cov.: 32 AF XY: 0.248 AC XY: 18428 AN XY: 74302

African (AFR) AF: 0.145 AC: 6036 AN: 41520

American (AMR) AF: 0.297 AC: 4537 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1095 AN: 3468

East Asian (EAS) AF: 0.269 AC: 1388 AN: 5164

South Asian (SAS) AF: 0.173 AC: 834 AN: 4822

European-Finnish (FIN) AF: 0.362 AC: 3818 AN: 10536

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18350 AN: 67970

Other (OTH) AF: 0.255 AC: 537 AN: 2110

Alfa AF: 0.260 Hom.: 859

Bravo AF: 0.233

Asia WGS AF: 0.227 AC: 788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.30
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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: rs1830756; hg19: chr13-108080223;