4-163148797-A-G

Variant names:

• chr4-163148797-A-G
• rs2320615
• NM_138386.3:c.541-363T>C

Variant summary

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

The NM_138386.3(NAF1):​c.541-363T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 152,082 control chromosomes in the GnomAD database, including 46,141 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 0.78 (46141 hom., cov: 33)
• Consequence: NAF1 NM_138386.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.504
• Publications: 7 publications found

Genes affected

NAF1 (HGNC:25126): (nuclear assembly factor 1 ribonucleoprotein) Enables identical protein binding activity and telomerase RNA binding activity. Involved in regulation of nucleobase-containing compound metabolic process; ribosome biogenesis; and telomerase holoenzyme complex assembly. Located in nucleoplasm. Part of sno(s)RNA-containing ribonucleoprotein complex. [provided by Alliance of Genome Resources, Apr 2022]

NAF1 Gene-Disease associations (from GenCC):

• pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAF1	NM_138386.3	c.541-363T>C		intron_variant	Intron 2 of 7	ENST00000274054.3	NP_612395.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAF1	ENST00000274054.3	c.541-363T>C		intron_variant	Intron 2 of 7	1	NM_138386.3	ENSP00000274054.2
NAF1	ENST00000422287.6	c.541-363T>C		intron_variant	Intron 2 of 7	1		ENSP00000408963.2
NAF1	ENST00000509232.5	n.645-363T>C		intron_variant	Intron 2 of 6	2

Frequencies

GnomAD3 genomes AF: 0.779 AC: 118340 AN: 151964 Hom.: 46114 Cov.: 33

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.750

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.841

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.774

Gnomad OTH AF: 0.761

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

GnomAD4 genome AF: 0.779 AC: 118421 AN: 152082 Hom.: 46141 Cov.: 33 AF XY: 0.782 AC XY: 58105 AN XY: 74348

African (AFR) AF: 0.774 AC: 32116 AN: 41508

American (AMR) AF: 0.788 AC: 12047 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 2602 AN: 3470

East Asian (EAS) AF: 0.788 AC: 4079 AN: 5176

South Asian (SAS) AF: 0.841 AC: 4064 AN: 4834

European-Finnish (FIN) AF: 0.811 AC: 8582 AN: 10586

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.774 AC: 52563 AN: 67908

Other (OTH) AF: 0.762 AC: 1610 AN: 2114

Alfa AF: 0.775 Hom.: 7091

Bravo AF: 0.773

Asia WGS AF: 0.836 AC: 2907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.3
DANN	Benign	0.85
PhyloP100		-0.50
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: rs2320615; hg19: chr4-164069949;