rs73998660

Variant names:

• chr17-77196230-A-G
• rs73998660
• NM_001143998.2:c.738A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001143998.2(SEC14L1):​c.738A>G​(p.Arg246Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00321 in 1,614,038 control chromosomes in the GnomAD database, including 154 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (90 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (64 hom.)
• Consequence: SEC14L1 NM_001143998.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.19
• Publications: 3 publications found

Genes affected

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 17-77196230-A-G is Benign according to our data. Variant chr17-77196230-A-G is described in ClinVar as Benign. ClinVar VariationId is 781390.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.19 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0585 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143998.2. 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_001143998.2	MANE Select	c.738A>G	p.Arg246Arg	synonymous	Exon 8 of 17	NP_001137470.2	Q92503-1
	SEC14L1	NM_001039573.3		c.738A>G	p.Arg246Arg	synonymous	Exon 8 of 18	NP_001034662.3	Q92503-2
	SEC14L1	NM_001204408.2		c.738A>G	p.Arg246Arg	synonymous	Exon 10 of 20	NP_001191337.2	Q92503-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC14L1	ENST00000436233.9	TSL:1 MANE Select	c.738A>G	p.Arg246Arg	synonymous	Exon 8 of 17	ENSP00000390392.3	Q92503-1
	SEC14L1	ENST00000443798.8	TSL:1	c.738A>G	p.Arg246Arg	synonymous	Exon 8 of 18	ENSP00000406030.3	Q92503-2
	SEC14L1	ENST00000585618.5	TSL:1	c.738A>G	p.Arg246Arg	synonymous	Exon 8 of 17	ENSP00000466581.1	Q92503-1

Frequencies

GnomAD3 genomes AF: 0.0174 AC: 2654 AN: 152170 Hom.: 88 Cov.: 32

Gnomad AFR AF: 0.0604

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00714

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.00445 AC: 1119 AN: 251312 AF XY: 0.00311

Gnomad AFR exome AF: 0.0606

Gnomad AMR exome AF: 0.00304

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00172 AC: 2511 AN: 1461750 Hom.: 64 Cov.: 30 AF XY: 0.00148 AC XY: 1075 AN XY: 727196

African (AFR) AF: 0.0599 AC: 2004 AN: 33456

American (AMR) AF: 0.00320 AC: 143 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00208 AC: 12 AN: 5766

European-Non Finnish (NFE) AF: 0.000120 AC: 133 AN: 1111924

Other (OTH) AF: 0.00353 AC: 213 AN: 60392

GnomAD4 genome AF: 0.0175 AC: 2663 AN: 152288 Hom.: 90 Cov.: 32 AF XY: 0.0165 AC XY: 1230 AN XY: 74462

African (AFR) AF: 0.0604 AC: 2511 AN: 41546

American (AMR) AF: 0.00713 AC: 109 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000220 AC: 15 AN: 68028

Other (OTH) AF: 0.0132 AC: 28 AN: 2116

Alfa AF: 0.00898 Hom.: 29

Bravo AF: 0.0201

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000178

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	-0.76
CADD	Benign	1.2
DANN	Benign	0.70
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs73998660; hg19: chr17-75192312;