rs8192326

Variant names:

• chr8-22162487-C-T
• rs8192326
• NM_001317778.2:c.43-87C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-22162487-C-T
• chr8-22162487-C-A
• chr8-22162487-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001317778.2(SFTPC):​c.43-87C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00356 in 1,473,346 control chromosomes in the GnomAD database, including 138 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (73 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (65 hom.)
• Consequence: SFTPC NM_001317778.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.97
• Publications: 0 publications found

Genes affected

SFTPC (HGNC:10802): (surfactant protein C) This gene encodes the pulmonary-associated surfactant protein C (SPC), an extremely hydrophobic surfactant protein essential for lung function and homeostasis after birth. Pulmonary surfactant is a surface-active lipoprotein complex composed of 90% lipids and 10% proteins which include plasma proteins and apolipoproteins SPA, SPB, SPC and SPD. The surfactant is secreted by the alveolar cells of the lung and maintains the stability of pulmonary tissue by reducing the surface tension of fluids that coat the lung. Multiple mutations in this gene have been identified, which cause pulmonary surfactant metabolism dysfunction type 2, also called pulmonary alveolar proteinosis due to surfactant protein C deficiency, and are associated with interstitial lung disease in older infants, children, and adults. Alternatively spliced transcript variants encoding different protein isoforms have been identified.[provided by RefSeq, Feb 2010]

SFTPC Gene-Disease associations (from GenCC):

• SFTPC-related interstitial lung disease

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• surfactant metabolism dysfunction, pulmonary, 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• chronic respiratory distress with surfactant metabolism deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 8-22162487-C-T is Benign according to our data. Variant chr8-22162487-C-T is described in ClinVar as Benign. ClinVar VariationId is 1293884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0614 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001317778.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFTPC	NM_001317778.2	MANE Select	c.43-87C>T		intron	N/A	NP_001304707.1	P11686-2
	SFTPC	NM_001172410.2		c.43-87C>T		intron	N/A	NP_001165881.1	A0A0S2Z4Q0
	SFTPC	NM_001385653.1		c.43-87C>T		intron	N/A	NP_001372582.1	P11686-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFTPC	ENST00000679463.1	MANE Select	c.43-87C>T		intron	N/A	ENSP00000505152.1	P11686-2
	SFTPC	ENST00000318561.7	TSL:1	c.43-87C>T		intron	N/A	ENSP00000316152.3	P11686-1
	SFTPC	ENST00000521315.5	TSL:1	c.43-87C>T		intron	N/A	ENSP00000430410.1	P11686-2

Frequencies

GnomAD3 genomes AF: 0.0183 AC: 2787 AN: 152182 Hom.: 72 Cov.: 33

Gnomad AFR AF: 0.0634

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0148

GnomAD4 exome AF: 0.00186 AC: 2452 AN: 1321046 Hom.: 65 AF XY: 0.00158 AC XY: 1047 AN XY: 664282

African (AFR) AF: 0.0628 AC: 1889 AN: 30098

American (AMR) AF: 0.00415 AC: 185 AN: 44562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25254

East Asian (EAS) AF: 0.00 AC: 0 AN: 38924

South Asian (SAS) AF: 0.000277 AC: 23 AN: 83180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50858

Middle Eastern (MID) AF: 0.00331 AC: 13 AN: 3932

European-Non Finnish (NFE) AF: 0.0000759 AC: 75 AN: 988694

Other (OTH) AF: 0.00481 AC: 267 AN: 55544

GnomAD4 genome AF: 0.0183 AC: 2794 AN: 152300 Hom.: 73 Cov.: 33 AF XY: 0.0181 AC XY: 1350 AN XY: 74478

African (AFR) AF: 0.0634 AC: 2635 AN: 41540

American (AMR) AF: 0.00719 AC: 110 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68024

Other (OTH) AF: 0.0147 AC: 31 AN: 2114

Alfa AF: 0.0131 Hom.: 1

Bravo AF: 0.0211

Asia WGS AF: 0.00346 AC: 13 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.085
DANN	Benign	0.43
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism

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: rs8192326; hg19: chr8-22020000;