chr2-85668581-C-T

Variant names:

• chr2-85668581-C-T
• rs3024791
• ENST00000393822.7:c.-69+93G>A

Variant summary

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

The NM_198843.3(SFTPB):​c.-69+93G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 275,172 control chromosomes in the GnomAD database, including 3,523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2353 hom., cov: 33)
  • Exomes 𝑓: 0.13 (1170 hom.)
• Consequence: SFTPB NM_198843.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.589
• Publications: 18 publications found

Genes affected

SFTPB (HGNC:10801): (surfactant protein B) This gene encodes the pulmonary-associated surfactant protein B (SPB), an amphipathic 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. The SPB enhances the rate of spreading and increases the stability of surfactant monolayers in vitro. Multiple mutations in this gene have been identified, which cause pulmonary surfactant metabolism dysfunction type 1, also called pulmonary alveolar proteinosis due to surfactant protein B deficiency, and are associated with fatal respiratory distress in the neonatal period. Alternatively spliced transcript variants encoding the same protein have been identified.[provided by RefSeq, Feb 2010]

SFTPB Gene-Disease associations (from GenCC):

• surfactant metabolism dysfunction, pulmonary, 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 2-85668581-C-T is Benign according to our data. Variant chr2-85668581-C-T is described in ClinVar as Benign. ClinVar VariationId is 1271864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198843.3. 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
	SFTPB	NM_198843.3		c.-69+93G>A		intron	N/A	NP_942140.3	P07988

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFTPB	ENST00000393822.7	TSL:1	c.-69+93G>A		intron	N/A	ENSP00000377409.4	P07988
	SFTPB	ENST00000409383.7	TSL:1	c.-69+93G>A		intron	N/A	ENSP00000386346.2
	SFTPB	ENST00000860672.1		c.-69+93G>A		intron	N/A	ENSP00000530731.1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24857 AN: 152144 Hom.: 2348 Cov.: 33

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.0842

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.0935

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.156

GnomAD4 exome AF: 0.126 AC: 15501 AN: 122910 Hom.: 1170 AF XY: 0.130 AC XY: 8236 AN XY: 63372

African (AFR) AF: 0.236 AC: 1034 AN: 4390

American (AMR) AF: 0.101 AC: 621 AN: 6168

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 527 AN: 3778

East Asian (EAS) AF: 0.0606 AC: 501 AN: 8272

South Asian (SAS) AF: 0.176 AC: 1893 AN: 10748

European-Finnish (FIN) AF: 0.0878 AC: 681 AN: 7760

Middle Eastern (MID) AF: 0.142 AC: 75 AN: 530

European-Non Finnish (NFE) AF: 0.124 AC: 9191 AN: 73898

Other (OTH) AF: 0.133 AC: 978 AN: 7366

GnomAD4 genome AF: 0.163 AC: 24890 AN: 152262 Hom.: 2353 Cov.: 33 AF XY: 0.162 AC XY: 12043 AN XY: 74466

African (AFR) AF: 0.249 AC: 10363 AN: 41542

American (AMR) AF: 0.126 AC: 1931 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 546 AN: 3472

East Asian (EAS) AF: 0.0840 AC: 435 AN: 5180

South Asian (SAS) AF: 0.203 AC: 982 AN: 4830

European-Finnish (FIN) AF: 0.0935 AC: 993 AN: 10616

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9142 AN: 68000

Other (OTH) AF: 0.154 AC: 326 AN: 2116

Alfa AF: 0.144 Hom.: 2495

Bravo AF: 0.170

Asia WGS AF: 0.153 AC: 534 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	-0.56
CADD	Benign	15
DANN	Benign	0.71
PhyloP100		0.59
PromoterAI		-0.058	Neutral
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: rs3024791; hg19: chr2-85895704;