rs2245121

Variant names:

• chr10-79939482-G-A
• rs2245121
• NM_003019.5:c.751+1223C>T

Variant summary

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

The NM_003019.5(SFTPD):​c.751+1223C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 152,140 control chromosomes in the GnomAD database, including 18,426 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 0.48 (18426 hom., cov: 33)
• Consequence: SFTPD NM_003019.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.893
• Publications: 15 publications found

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]

ENSG00000283913 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003019.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFTPD	NM_003019.5	MANE Select	c.751+1223C>T		intron	N/A	NP_003010.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFTPD	ENST00000372292.8	TSL:1 MANE Select	c.751+1223C>T		intron	N/A	ENSP00000361366.3
	ENSG00000283913	ENST00000421889.1	TSL:3	n.235-1955G>A		intron	N/A
	ENSG00000283913	ENST00000453174.7	TSL:2	n.961+2826G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73057 AN: 152022 Hom.: 18414 Cov.: 33

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.761

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.447

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.481 AC: 73110 AN: 152140 Hom.: 18426 Cov.: 33 AF XY: 0.482 AC XY: 35849 AN XY: 74352

African (AFR) AF: 0.580 AC: 24072 AN: 41482

American (AMR) AF: 0.349 AC: 5337 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1251 AN: 3468

East Asian (EAS) AF: 0.761 AC: 3936 AN: 5174

South Asian (SAS) AF: 0.490 AC: 2366 AN: 4830

European-Finnish (FIN) AF: 0.483 AC: 5106 AN: 10578

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.434 AC: 29481 AN: 67986

Other (OTH) AF: 0.447 AC: 946 AN: 2114

Alfa AF: 0.432 Hom.: 16619

Bravo AF: 0.475

Asia WGS AF: 0.588 AC: 2045 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.034
DANN	Benign	0.61
PhyloP100		-0.89
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: rs2245121; hg19: chr10-81699238;