rs72659390

Variant names:

• chr10-79611942-C-T
• rs72659390
• NM_005411.5:c.117C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005411.5(SFTPA1):​c.117C>T​(p.His39His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,613,662 control chromosomes in the GnomAD database, including 15,085 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1289 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13796 hom.)
• Consequence: SFTPA1 NM_005411.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.95
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 10-79611942-C-T is Benign according to our data. Variant chr10-79611942-C-T is described in ClinVar as Benign. ClinVar VariationId is 227061.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.95 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.199 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.117C>T	p.His39His	synonymous	Exon 3 of 6	NP_005402.3
	SFTPA1	NM_001093770.3		c.162C>T	p.His54His	synonymous	Exon 3 of 6	NP_001087239.2	Q8IWL2-2
	SFTPA1	NM_001164644.2		c.117C>T	p.His39His	synonymous	Exon 3 of 6	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.117C>T	p.His39His	synonymous	Exon 3 of 6	ENSP00000381633.3	Q8IWL2-1
	SFTPA1	ENST00000419470.6	TSL:1	c.162C>T	p.His54His	synonymous	Exon 3 of 6	ENSP00000397082.2	Q8IWL2-2
	SFTPA1	ENST00000428376.6	TSL:1	c.117C>T	p.His39His	synonymous	Exon 2 of 5	ENSP00000411102.2	Q8IWL2-1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19044 AN: 151980 Hom.: 1288 Cov.: 32

Gnomad AFR AF: 0.0993

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.0907

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.124

GnomAD2 exomes AF: 0.142 AC: 35584 AN: 250976 AF XY: 0.149

Gnomad AFR exome AF: 0.0958

Gnomad AMR exome AF: 0.0817

Gnomad ASJ exome AF: 0.197

Gnomad EAS exome AF: 0.212

Gnomad FIN exome AF: 0.160

Gnomad NFE exome AF: 0.125

Gnomad OTH exome AF: 0.131

GnomAD4 exome AF: 0.131 AC: 191713 AN: 1461564 Hom.: 13796 Cov.: 108 AF XY: 0.135 AC XY: 98271 AN XY: 727086

African (AFR) AF: 0.0949 AC: 3176 AN: 33470

American (AMR) AF: 0.0836 AC: 3736 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 5215 AN: 26130

East Asian (EAS) AF: 0.221 AC: 8786 AN: 39696

South Asian (SAS) AF: 0.224 AC: 19281 AN: 86236

European-Finnish (FIN) AF: 0.162 AC: 8649 AN: 53414

Middle Eastern (MID) AF: 0.214 AC: 1228 AN: 5748

European-Non Finnish (NFE) AF: 0.120 AC: 133551 AN: 1111786

Other (OTH) AF: 0.134 AC: 8091 AN: 60374

GnomAD4 genome AF: 0.125 AC: 19050 AN: 152098 Hom.: 1289 Cov.: 32 AF XY: 0.128 AC XY: 9532 AN XY: 74356

African (AFR) AF: 0.0992 AC: 4118 AN: 41520

American (AMR) AF: 0.0907 AC: 1386 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 682 AN: 3466

East Asian (EAS) AF: 0.206 AC: 1059 AN: 5144

South Asian (SAS) AF: 0.210 AC: 1012 AN: 4826

European-Finnish (FIN) AF: 0.157 AC: 1660 AN: 10596

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8757 AN: 67946

Other (OTH) AF: 0.124 AC: 262 AN: 2110

Alfa AF: 0.139 Hom.: 518

Bravo AF: 0.114

Asia WGS AF: 0.196 AC: 681 AN: 3478

EpiCase AF: 0.138

EpiControl AF: 0.133

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	not provided (1)
-	-	1	SFTPA1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.1
DANN	Benign	0.61
PhyloP100		-2.0
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: rs72659390; hg19: chr10-81371698; COSMIC: COSV64866713; COSMIC: COSV64866713;