rs16969969

chr13-107301929-C-Achr13-107301929-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080396.3(NALF1):c.916-91174G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0442 in 152,186 control chromosomes in the GnomAD database, including 213 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 0.044 (213 hom., cov: 33)
• Consequence: NALF1 NM_001080396.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.890

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NALF1	NM_001080396.3	c.916-91174G>T		intron_variant		ENST00000375915.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NALF1	ENST00000375915.4	c.916-91174G>T		intron_variant		1	NM_001080396.3	P1

Frequencies

GnomAD3 genomes AF: 0.0443 AC: 6730 AN: 152068 Hom.: 213 Cov.: 33

Gnomad AFR AF: 0.0201

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.0738

Gnomad ASJ AF: 0.0369

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.0485

Gnomad FIN AF: 0.0219

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.0460

Gnomad OTH AF: 0.0568

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

GnomAD4 genome AF: 0.0442 AC: 6730 AN: 152186 Hom.: 213 Cov.: 33 AF XY: 0.0454 AC XY: 3376 AN XY: 74376

Gnomad4 AFR AF: 0.0202

Gnomad4 AMR AF: 0.0737

Gnomad4 ASJ AF: 0.0369

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.0489

Gnomad4 FIN AF: 0.0219

Gnomad4 NFE AF: 0.0460

Gnomad4 OTH AF: 0.0558

Alfa AF: 0.0140 Hom.: 6

Bravo AF: 0.0493

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.0
Dann	Benign	0.55

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

LitVar

Other links and lift over

dbSNP: rs16969969; hg19: chr13-107954277;