NM_005411.5:c.173-115C>T

Variant names:

• chr10-79612197-C-T
• rs1914663
• NM_005411.5:c.173-115C>T

Variant summary

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

The NM_005411.5(SFTPA1):​c.173-115C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0923 in 1,605,492 control chromosomes in the GnomAD database, including 7,613 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 0.11 (1081 hom., cov: 32)
  • Exomes 𝑓: 0.090 (6532 hom.)
• Consequence: SFTPA1 NM_005411.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 9 publications found

Genes affected

SFTPA1 (HGNC:10798): (surfactant protein A1) This gene encodes a lung surfactant protein that is a member of a subfamily of C-type lectins called collectins. The encoded protein binds specific carbohydrate moieties found on lipids and on the surface of microorganisms. This protein plays an essential role in surfactant homeostasis and in the defense against respiratory pathogens. Mutations in this gene are associated with idiopathic pulmonary fibrosis. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

SFTPA1 Gene-Disease associations (from GenCC):

• interstitial lung disease 1

  Inheritance: AD, SD Classification: STRONG, MODERATE Submitted by: ClinGen, PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005411.5. 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
	SFTPA1	NM_005411.5	MANE Select	c.173-115C>T		intron	N/A	NP_005402.3
	SFTPA1	NM_001093770.3		c.218-115C>T		intron	N/A	NP_001087239.2	Q8IWL2-2
	SFTPA1	NM_001164644.2		c.173-115C>T		intron	N/A	NP_001158116.1	Q8IWL2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFTPA1	ENST00000398636.8	TSL:1 MANE Select	c.173-115C>T		intron	N/A	ENSP00000381633.3	Q8IWL2-1
	SFTPA1	ENST00000419470.6	TSL:1	c.218-115C>T		intron	N/A	ENSP00000397082.2	Q8IWL2-2
	SFTPA1	ENST00000428376.6	TSL:1	c.173-115C>T		intron	N/A	ENSP00000411102.2	Q8IWL2-1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16923 AN: 152004 Hom.: 1081 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.0736

Gnomad FIN AF: 0.0985

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.0877

Gnomad OTH AF: 0.128

GnomAD4 exome AF: 0.0903 AC: 131242 AN: 1453370 Hom.: 6532 AF XY: 0.0895 AC XY: 64726 AN XY: 723188

African (AFR) AF: 0.138 AC: 4597 AN: 33284

American (AMR) AF: 0.0949 AC: 4234 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 3705 AN: 25884

East Asian (EAS) AF: 0.224 AC: 8882 AN: 39642

South Asian (SAS) AF: 0.0646 AC: 5491 AN: 85046

European-Finnish (FIN) AF: 0.108 AC: 5723 AN: 53202

Middle Eastern (MID) AF: 0.113 AC: 503 AN: 4438

European-Non Finnish (NFE) AF: 0.0828 AC: 91708 AN: 1107206

Other (OTH) AF: 0.107 AC: 6399 AN: 60030

GnomAD4 genome AF: 0.111 AC: 16951 AN: 152122 Hom.: 1081 Cov.: 32 AF XY: 0.113 AC XY: 8410 AN XY: 74350

African (AFR) AF: 0.137 AC: 5671 AN: 41488

American (AMR) AF: 0.114 AC: 1745 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 512 AN: 3468

East Asian (EAS) AF: 0.240 AC: 1236 AN: 5158

South Asian (SAS) AF: 0.0738 AC: 356 AN: 4822

European-Finnish (FIN) AF: 0.0985 AC: 1043 AN: 10590

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0877 AC: 5964 AN: 67994

Other (OTH) AF: 0.131 AC: 275 AN: 2106

Alfa AF: 0.0981 Hom.: 88

Bravo AF: 0.115

Asia WGS AF: 0.162 AC: 562 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.13
DANN	Benign	0.53
PhyloP100		-1.4
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: rs1914663; hg19: chr10-81371953; COSMIC: COSV64867546; COSMIC: COSV64867546;