rs17848327

Variant names:

• chr9-128350297-G-A
• rs17848327
• NM_005094.4:c.716-15G>A

Variant summary

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

The NM_005094.4(SLC27A4):​c.716-15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00383 in 1,612,074 control chromosomes in the GnomAD database, including 244 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (17 hom., cov: 33)
  • Exomes 𝑓: 0.0039 (227 hom.)
• Consequence: SLC27A4 NM_005094.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.345
• Publications: 3 publications found

Genes affected

SLC27A4 (HGNC:10998): (solute carrier family 27 member 4) This gene encodes a member of a family of fatty acid transport proteins, which are involved in translocation of long-chain fatty acids cross the plasma membrane. This protein is expressed at high levels on the apical side of mature enterocytes in the small intestine, and appears to be the principal fatty acid transporter in enterocytes. Clinical studies suggest this gene as a candidate gene for the insulin resistance syndrome. Mutations in this gene have been associated with ichthyosis prematurity syndrome. [provided by RefSeq, Apr 2010]

SLC27A4 Gene-Disease associations (from GenCC):

• ichthyosis prematurity syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, PanelApp Australia, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 9-128350297-G-A is Benign according to our data. Variant chr9-128350297-G-A is described in ClinVar as Benign. ClinVar VariationId is 1665394.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.077 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005094.4. 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
	SLC27A4	NM_005094.4	MANE Select	c.716-15G>A		intron	N/A	NP_005085.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC27A4	ENST00000300456.5	TSL:1 MANE Select	c.716-15G>A		intron	N/A	ENSP00000300456.3
	SLC27A4	ENST00000372870.5	TSL:1	c.232-4881G>A		intron	N/A	ENSP00000361961.1

Frequencies

GnomAD3 genomes AF: 0.00367 AC: 559 AN: 152210 Hom.: 17 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0837

Gnomad SAS AF: 0.0159

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00829 AC: 2051 AN: 247544 AF XY: 0.00780

Gnomad AFR exome AF: 0.000195

Gnomad AMR exome AF: 0.000232

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0787

Gnomad FIN exome AF: 0.00236

Gnomad NFE exome AF: 0.000261

Gnomad OTH exome AF: 0.00527

GnomAD4 exome AF: 0.00385 AC: 5624 AN: 1459746 Hom.: 227 Cov.: 32 AF XY: 0.00392 AC XY: 2849 AN XY: 726196

African (AFR) AF: 0.000239 AC: 8 AN: 33458

American (AMR) AF: 0.000157 AC: 7 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0957 AC: 3800 AN: 39688

South Asian (SAS) AF: 0.0129 AC: 1115 AN: 86164

European-Finnish (FIN) AF: 0.00199 AC: 104 AN: 52332

Middle Eastern (MID) AF: 0.00154 AC: 8 AN: 5198

European-Non Finnish (NFE) AF: 0.000162 AC: 180 AN: 1111736

Other (OTH) AF: 0.00666 AC: 402 AN: 60316

GnomAD4 genome AF: 0.00366 AC: 557 AN: 152328 Hom.: 17 Cov.: 33 AF XY: 0.00431 AC XY: 321 AN XY: 74484

African (AFR) AF: 0.000168 AC: 7 AN: 41574

American (AMR) AF: 0.000523 AC: 8 AN: 15302

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

East Asian (EAS) AF: 0.0835 AC: 432 AN: 5172

South Asian (SAS) AF: 0.0159 AC: 77 AN: 4828

European-Finnish (FIN) AF: 0.00151 AC: 16 AN: 10624

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

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68034

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.000975 Hom.: 1

Bravo AF: 0.00321

Asia WGS AF: 0.0490 AC: 170 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.86
CADD	Benign	1.3
DANN	Benign	0.83
PhyloP100		-0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs17848327; hg19: chr9-131112576; COSMIC: COSV55959304;