10-79938243-AAGTC-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_003019.5(SFTPD):c.752-19_752-16del variant causes a splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.0852 in 1,575,720 control chromosomes in the GnomAD database, including 7,328 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1688 hom., cov: 30)
  • Exomes 𝑓: 0.081 (5640 hom.)
• Consequence: SFTPD NM_003019.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.61

Genes affected

SFTPD (HGNC:10803): (surfactant protein D) The protein encoded by this gene is part of the innate immune response, protecting the lungs against inhaled microorganisms and chemicals. The encoded protein may also be involved in surfactant metabolism. [provided by RefSeq, Jul 2015]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 10-79938243-AAGTC-A is Benign according to our data. Variant chr10-79938243-AAGTC-A is described in ClinVar as [Benign]. Clinvar id is 403430.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFTPD	NM_003019.5	c.752-19_752-16del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000372292.8
SFTPD	XM_011540087.2	c.752-19_752-16del		splice_polypyrimidine_tract_variant, intron_variant
SFTPD	XM_011540088.3	c.635-19_635-16del		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFTPD	ENST00000372292.8	c.752-19_752-16del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_003019.5	P1
	ENST00000421889.1	n.234+1590_234+1593del		intron_variant, non_coding_transcript_variant		3
SFTPD	ENST00000678361.1	n.2957-19_2957-16del		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant
SFTPD	ENST00000679234.1	n.2878-19_2878-16del		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18768 AN: 151938 Hom.: 1688 Cov.: 30

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.0764

Gnomad ASJ AF: 0.0283

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0207

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0807

Gnomad OTH AF: 0.108

GnomAD3 exomes AF: 0.0778 AC: 18138 AN: 233108 Hom.: 1097 AF XY: 0.0737 AC XY: 9277 AN XY: 125846

Gnomad AFR exome AF: 0.252

Gnomad AMR exome AF: 0.0518

Gnomad ASJ exome AF: 0.0300

Gnomad EAS exome AF: 0.000606

Gnomad SAS exome AF: 0.0227

Gnomad FIN exome AF: 0.133

Gnomad NFE exome AF: 0.0829

Gnomad OTH exome AF: 0.0754

GnomAD4 exome AF: 0.0811 AC: 115456 AN: 1423664 Hom.: 5640 AF XY: 0.0783 AC XY: 54945 AN XY: 702012

Gnomad4 AFR exome AF: 0.253

Gnomad4 AMR exome AF: 0.0543

Gnomad4 ASJ exome AF: 0.0293

Gnomad4 EAS exome AF: 0.000743

Gnomad4 SAS exome AF: 0.0221

Gnomad4 FIN exome AF: 0.127

Gnomad4 NFE exome AF: 0.0835

Gnomad4 OTH exome AF: 0.0829

GnomAD4 genome AF: 0.123 AC: 18772 AN: 152056 Hom.: 1688 Cov.: 30 AF XY: 0.121 AC XY: 9004 AN XY: 74322

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.0762

Gnomad4 ASJ AF: 0.0283

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0205

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.0807

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0938 Hom.: 181

Bravo AF: 0.128

Asia WGS AF: 0.0310 AC: 110 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs17880072; hg19: chr10-81697999;