rs2304927

Variant names:

• chr17-77088760-G-A
• rs2304927
• ENST00000434411.6:n.130G>A

Variant summary

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

The NM_001204408.2(SEC14L1):​c.-548G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0378 in 149,106 control chromosomes in the GnomAD database, including 192 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 0.038 (192 hom., cov: 32)
  • Exomes 𝑓: 0.045 (0 hom.)
• Consequence: SEC14L1 NM_001204408.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.569
• Publications: 5 publications found

Genes affected

SNHG20 (HGNC:33099): (small nucleolar RNA host gene 20)

SEC14L1 (HGNC:10698): (SEC14 like lipid binding 1) The protein encoded by this gene belongs to the SEC14 cytosolic factor family. It has similarity to yeast SEC14 and to Japanese flying squid RALBP which suggests a possible role of the gene product in an intracellular transport system. Multiple alternatively spliced transcript variants have been found for this gene; some variants represent read-through transcripts that include exons from the upstream gene C17orf86. [provided by RefSeq, Feb 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001204408.2. 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
	SEC14L1	NM_001204408.2		c.-548G>A		5_prime_UTR	Exon 1 of 20	NP_001191337.2	Q92503-2
	SEC14L1	NM_001204410.2		c.-548G>A		5_prime_UTR	Exon 1 of 19	NP_001191339.2	Q92503-1
	SNHG20	NR_027058.1		n.118G>A		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNHG20	ENST00000434411.6	TSL:1	n.130G>A		non_coding_transcript_exon	Exon 1 of 3
	SNHG20	ENST00000561633.5	TSL:1	n.12G>A		non_coding_transcript_exon	Exon 1 of 4
	SNHG20	ENST00000564509.5	TSL:1	n.12G>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.0378 AC: 5629 AN: 148874 Hom.: 194 Cov.: 32

Gnomad AFR AF: 0.0122

Gnomad AMI AF: 0.0673

Gnomad AMR AF: 0.0219

Gnomad ASJ AF: 0.0601

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.0264

Gnomad FIN AF: 0.0463

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.0417

Gnomad OTH AF: 0.0397

GnomAD4 exome AF: 0.0446 AC: 5 AN: 112 Hom.: 0 Cov.: 0 AF XY: 0.0581 AC XY: 5 AN XY: 86

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.167 AC: 1 AN: 6

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0222 AC: 2 AN: 90

Other (OTH) AF: 0.333 AC: 2 AN: 6

GnomAD4 genome AF: 0.0378 AC: 5629 AN: 148994 Hom.: 192 Cov.: 32 AF XY: 0.0381 AC XY: 2771 AN XY: 72732

African (AFR) AF: 0.0123 AC: 497 AN: 40374

American (AMR) AF: 0.0219 AC: 327 AN: 14920

Ashkenazi Jewish (ASJ) AF: 0.0601 AC: 204 AN: 3394

East Asian (EAS) AF: 0.210 AC: 1051 AN: 5008

South Asian (SAS) AF: 0.0257 AC: 119 AN: 4622

European-Finnish (FIN) AF: 0.0463 AC: 482 AN: 10410

Middle Eastern (MID) AF: 0.0411 AC: 12 AN: 292

European-Non Finnish (NFE) AF: 0.0417 AC: 2794 AN: 67004

Other (OTH) AF: 0.0397 AC: 82 AN: 2064

Alfa AF: 0.0394 Hom.: 28

Bravo AF: 0.0367

Asia WGS AF: 0.0920 AC: 319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.9
DANN	Benign	0.81
PhyloP100		-0.57
PromoterAI		-0.081	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2304927; hg19: chr17-75084842;