rs1136450

Variant names:

• chr10-79611973-C-G
• rs1136450
• NM_005411.5:c.148C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-79611973-C-G
• chr10-79611973-C-A

Variant summary

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

The NM_005411.5(SFTPA1):​c.148C>G​(p.Leu50Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 1,322,774 control chromosomes in the GnomAD database, including 258,923 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (20962 hom., cov: 29)
  • Exomes 𝑓: 0.57 (237961 hom.)
• Consequence: SFTPA1 NM_005411.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.893
• Publications: 39 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.2757053E-4).
• BP6: Variant 10-79611973-C-G is Benign according to our data. Variant chr10-79611973-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 227062.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.582 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.148C>G	p.Leu50Val	missense	Exon 3 of 6	NP_005402.3
	SFTPA1	NM_001093770.3		c.193C>G	p.Leu65Val	missense	Exon 3 of 6	NP_001087239.2	Q8IWL2-2
	SFTPA1	NM_001164644.2		c.148C>G	p.Leu50Val	missense	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.148C>G	p.Leu50Val	missense	Exon 3 of 6	ENSP00000381633.3	Q8IWL2-1
	SFTPA1	ENST00000419470.6	TSL:1	c.193C>G	p.Leu65Val	missense	Exon 3 of 6	ENSP00000397082.2	Q8IWL2-2
	SFTPA1	ENST00000428376.6	TSL:1	c.148C>G	p.Leu50Val	missense	Exon 2 of 5	ENSP00000411102.2	Q8IWL2-1

Frequencies

GnomAD3 genomes AF: 0.521 AC: 78464 AN: 150688 Hom.: 20968 Cov.: 29

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.480

GnomAD2 exomes AF: 0.494 AC: 117251 AN: 237278 AF XY: 0.492

Gnomad AFR exome AF: 0.454

Gnomad AMR exome AF: 0.435

Gnomad ASJ exome AF: 0.431

Gnomad EAS exome AF: 0.266

Gnomad FIN exome AF: 0.563

Gnomad NFE exome AF: 0.583

Gnomad OTH exome AF: 0.503

GnomAD4 exome AF: 0.573 AC: 671034 AN: 1171968 Hom.: 237961 Cov.: 66 AF XY: 0.565 AC XY: 333686 AN XY: 591048

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.450 AC: 12439 AN: 27670

American (AMR) AF: 0.439 AC: 19005 AN: 43320

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 10325 AN: 24088

East Asian (EAS) AF: 0.304 AC: 11214 AN: 36890

South Asian (SAS) AF: 0.363 AC: 29027 AN: 79926

European-Finnish (FIN) AF: 0.562 AC: 28885 AN: 51354

Middle Eastern (MID) AF: 0.342 AC: 1742 AN: 5088

European-Non Finnish (NFE) AF: 0.623 AC: 531464 AN: 852770

Other (OTH) AF: 0.530 AC: 26933 AN: 50862

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.520 AC: 78474 AN: 150806 Hom.: 20962 Cov.: 29 AF XY: 0.512 AC XY: 37708 AN XY: 73612

African (AFR) AF: 0.470 AC: 19316 AN: 41112

American (AMR) AF: 0.466 AC: 7087 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1524 AN: 3454

East Asian (EAS) AF: 0.290 AC: 1465 AN: 5048

South Asian (SAS) AF: 0.354 AC: 1682 AN: 4752

European-Finnish (FIN) AF: 0.575 AC: 6025 AN: 10472

Middle Eastern (MID) AF: 0.432 AC: 126 AN: 292

European-Non Finnish (NFE) AF: 0.587 AC: 39593 AN: 67496

Other (OTH) AF: 0.475 AC: 990 AN: 2084

Alfa AF: 0.518 Hom.: 3611

Bravo AF: 0.515

ExAC AF: 0.496 AC: 60242

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)
-	-	1	SFTPA1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.040
DANN	Benign	0.18
DEOGEN2	Benign	0.047	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0026	N
LIST_S2	Benign	0.17	T
MetaRNN	Benign	0.00023	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.60	N
PhyloP100		-0.89
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.58	N
REVEL	Benign	0.021
Sift	Benign	1.0	T
Sift4G	Benign	0.73	T
Polyphen		0.0	B
Vest4		0.069
MPC		0.017
ClinPred		0.0099	T
GERP RS		-3.0
Varity_R		0.036
gMVP		0.096
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: rs1136450; hg19: chr10-81371729; COSMIC: COSV64866550; COSMIC: COSV64866550;