NM_001080396.3:c.915+189853A>G

Variant names:

• chr13-107675829-T-C
• rs1935135
• NM_001080396.3:c.915+189853A>G

Variant summary

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

The NM_001080396.3(NALF1):​c.915+189853A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,098 control chromosomes in the GnomAD database, including 6,045 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 0.27 (6045 hom., cov: 32)
• Consequence: NALF1 NM_001080396.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NALF1	NM_001080396.3	c.915+189853A>G		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.915+189853A>G		intron_variant	Intron 1 of 2	1	NM_001080396.3	ENSP00000365080.1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40825 AN: 151980 Hom.: 6053 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.268 AC: 40818 AN: 152098 Hom.: 6045 Cov.: 32 AF XY: 0.266 AC XY: 19780 AN XY: 74362

African (AFR) AF: 0.141 AC: 5845 AN: 41508

American (AMR) AF: 0.290 AC: 4425 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1270 AN: 3466

East Asian (EAS) AF: 0.451 AC: 2327 AN: 5162

South Asian (SAS) AF: 0.285 AC: 1372 AN: 4820

European-Finnish (FIN) AF: 0.283 AC: 2995 AN: 10592

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21693 AN: 67954

Other (OTH) AF: 0.272 AC: 575 AN: 2114

Alfa AF: 0.303 Hom.: 24484

Bravo AF: 0.266

Asia WGS AF: 0.361 AC: 1258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.56
PhyloP100		-0.38
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: rs1935135; hg19: chr13-108328177;