14-23147985-G-C

Position:

• chr14-23147985-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012244.4(SLC7A8):​c.509-4781C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 152,088 control chromosomes in the GnomAD database, including 49,538 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 0.81 (49538 hom., cov: 31)
• Consequence: SLC7A8 NM_012244.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

Genes affected

SLC7A8 (HGNC:11066): (solute carrier family 7 member 8) Enables several functions, including neutral amino acid transmembrane transporter activity; thyroid hormone transmembrane transporter activity; and toxin transmembrane transporter activity. Involved in L-alanine import across plasma membrane; L-leucine import across plasma membrane; and thyroid hormone transport. Located in plasma membrane. Part of basolateral plasma membrane and microvillus membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A8	NM_012244.4	c.509-4781C>G		intron_variant		ENST00000316902.12	NP_036376.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC7A8	ENST00000316902.12	c.509-4781C>G		intron_variant		1	NM_012244.4	ENSP00000320378	P1

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122441 AN: 151970 Hom.: 49489 Cov.: 31

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.832

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.800

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

GnomAD4 genome AF: 0.806 AC: 122545 AN: 152088 Hom.: 49538 Cov.: 31 AF XY: 0.806 AC XY: 59897 AN XY: 74340

Gnomad4 AFR AF: 0.838

Gnomad4 AMR AF: 0.832

Gnomad4 ASJ AF: 0.791

Gnomad4 EAS AF: 0.905

Gnomad4 SAS AF: 0.729

Gnomad4 FIN AF: 0.799

Gnomad4 NFE AF: 0.780

Gnomad4 OTH AF: 0.802

Alfa AF: 0.748 Hom.: 2281

Bravo AF: 0.814

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.18
DANN	Benign	0.53

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: rs12588118; hg19: chr14-23617194;