5-135535750-A-C

Variant names:

• chr5-135535750-A-C
• rs8192558
• NM_006161.3:c.-60T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

ENSG00000250167 (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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006161.3. 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
	NEUROG1	NM_006161.3	MANE Select	c.-60T>G		5_prime_UTR	Exon 1 of 1	NP_006152.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEUROG1	ENST00000314744.6	TSL:6 MANE Select	c.-60T>G		5_prime_UTR	Exon 1 of 1	ENSP00000317580.4
	ENSG00000250167	ENST00000698884.1		n.496+48981A>C		intron	N/A
	SLC25A48	ENST00000698885.1		n.364+25994A>C		intron	N/A

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

African (AFR) AF: 0.0931 AC: 2346 AN: 25192

American (AMR) AF: 0.205 AC: 4659 AN: 22764

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 5002 AN: 18268

East Asian (EAS) AF: 0.204 AC: 6839 AN: 33564

South Asian (SAS) AF: 0.244 AC: 15390 AN: 62994

European-Finnish (FIN) AF: 0.198 AC: 9450 AN: 47826

Middle Eastern (MID) AF: 0.255 AC: 1174 AN: 4604

European-Non Finnish (NFE) AF: 0.240 AC: 243150 AN: 1012422

Other (OTH) AF: 0.236 AC: 12475 AN: 52758

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

African (AFR) AF: 0.100 AC: 4154 AN: 41508

American (AMR) AF: 0.222 AC: 3404 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 951 AN: 3472

East Asian (EAS) AF: 0.205 AC: 1052 AN: 5132

South Asian (SAS) AF: 0.263 AC: 1264 AN: 4810

European-Finnish (FIN) AF: 0.188 AC: 1990 AN: 10592

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.238 AC: 16170 AN: 67956

Other (OTH) AF: 0.216 AC: 455 AN: 2106

Alfa AF: 0.219 Hom.: 2323

Bravo AF: 0.189

Asia WGS AF: 0.264 AC: 917 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	14
DANN	Benign	0.66
PhyloP100		0.29
PromoterAI		-0.00020	Neutral
Mutation Taster		=300/0	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: rs8192558; hg19: chr5-134871440; COSMIC: COSV59081802;