rs8192558

chr5-135535750-A-C

Variant summary

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

The NM_006161.3(NEUROG1):c.-60T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,432,470 control chromosomes in the GnomAD database, including 38,918 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 0.19 (3249 hom., cov: 33)
  • Exomes 𝑓: 0.23 (35669 hom.)
• Consequence: NEUROG1 NM_006161.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.294

Genes affected

NEUROG1 (HGNC:7764): (neurogenin 1) Enables E-box binding activity and protein homodimerization activity. Involved in several processes, including animal organ morphogenesis; cranial nerve development; and hard palate morphogenesis. Predicted to be located in neuronal cell body. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

SLC25A48 (HGNC:30451): (solute carrier family 25 member 48) Predicted to enable acyl carnitine transmembrane transporter activity. Predicted to be involved in acyl carnitine transport and amino acid transport. Predicted to be located in mitochondrial inner membrane. Predicted to be integral component of 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEUROG1	NM_006161.3	c.-60T>G		5_prime_UTR_variant	1/1	ENST00000314744.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEUROG1	ENST00000314744.6	c.-60T>G		5_prime_UTR_variant	1/1		NM_006161.3	P1
	ENST00000698884.1	n.496+48981A>C		intron_variant, non_coding_transcript_variant
SLC25A48	ENST00000698885.1	n.364+25994A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29615 AN: 151960 Hom.: 3248 Cov.: 33

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.214

GnomAD4 exome AF: 0.235 AC: 300485 AN: 1280392 Hom.: 35669 Cov.: 22 AF XY: 0.236 AC XY: 147875 AN XY: 627674

Gnomad4 AFR exome AF: 0.0931

Gnomad4 AMR exome AF: 0.205

Gnomad4 ASJ exome AF: 0.274

Gnomad4 EAS exome AF: 0.204

Gnomad4 SAS exome AF: 0.244

Gnomad4 FIN exome AF: 0.198

Gnomad4 NFE exome AF: 0.240

Gnomad4 OTH exome AF: 0.236

GnomAD4 genome AF: 0.195 AC: 29628 AN: 152078 Hom.: 3249 Cov.: 33 AF XY: 0.194 AC XY: 14451 AN XY: 74362

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.216

Alfa AF: 0.212 Hom.: 1476

Bravo AF: 0.189

Asia WGS AF: 0.264 AC: 917 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	14
Dann	Benign	0.66

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: rs8192558; hg19: chr5-134871440; COSMIC: COSV59081802;