rs2211312

Variant names:

• chr13-107753579-A-C
• rs2211312
• NM_001080396.3:c.915+112103T>G

Variant summary

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

The NM_001080396.3(NALF1):​c.915+112103T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 151,984 control chromosomes in the GnomAD database, including 1,775 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 0.14 (1775 hom., cov: 32)
• Consequence: NALF1 NM_001080396.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.541

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NALF1	NM_001080396.3	c.915+112103T>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+112103T>G		intron_variant	Intron 1 of 2	1	NM_001080396.3	ENSP00000365080.1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21549 AN: 151866 Hom.: 1766 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.0968

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.142 AC: 21572 AN: 151984 Hom.: 1775 Cov.: 32 AF XY: 0.148 AC XY: 11013 AN XY: 74284

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.0968

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.129

Alfa AF: 0.125 Hom.: 1645

Bravo AF: 0.147

Asia WGS AF: 0.192 AC: 668 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.3
DANN	Benign	0.31

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: rs2211312; hg19: chr13-108405927;