rs1053129

Variant names:

• chr5-80626901-C-A
• rs1053129
• NM_000791.4:c.*2186G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-80626901-C-A
• chr5-80626901-C-G
• chr5-80626901-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000791.4(DHFR):​c.*2186G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.27 (4457 hom., cov: 18)
  • Exomes 𝑓: 0.19 (218 hom.)
  • Failed GnomAD Quality Control
• Consequence: DHFR NM_000791.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 4 publications found

Genes affected

DHFR (HGNC:2861): (dihydrofolate reductase) Dihydrofolate reductase converts dihydrofolate into tetrahydrofolate, a methyl group shuttle required for the de novo synthesis of purines, thymidylic acid, and certain amino acids. While the functional dihydrofolate reductase gene has been mapped to chromosome 5, multiple intronless processed pseudogenes or dihydrofolate reductase-like genes have been identified on separate chromosomes. Dihydrofolate reductase deficiency has been linked to megaloblastic anemia. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2014]

DHFR Gene-Disease associations (from GenCC):

• constitutional megaloblastic anemia with severe neurologic disease

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHFR	NM_000791.4	c.*2186G>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000439211.7	NP_000782.1
DHFR	NR_110936.2	n.3067G>T		non_coding_transcript_exon_variant	Exon 4 of 4
DHFR	NM_001290354.2	c.*2186G>T		3_prime_UTR_variant	Exon 5 of 5		NP_001277283.1
DHFR	NM_001290357.2	c.*2244G>T		3_prime_UTR_variant	Exon 5 of 5		NP_001277286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHFR	ENST00000439211.7	c.*2186G>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_000791.4	ENSP00000396308.2

Frequencies

GnomAD3 genomes AF: 0.271 AC: 33009 AN: 121596 Hom.: 4454 Cov.: 18

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.0478

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.336

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.294

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.186 AC: 3437 AN: 18488 Hom.: 218 Cov.: 0 AF XY: 0.189 AC XY: 1617 AN XY: 8556

African (AFR) AF: 0.231 AC: 141 AN: 610

American (AMR) AF: 0.151 AC: 67 AN: 444

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 231 AN: 1104

East Asian (EAS) AF: 0.0155 AC: 60 AN: 3864

South Asian (SAS) AF: 0.287 AC: 35 AN: 122

European-Finnish (FIN) AF: 0.0714 AC: 1 AN: 14

Middle Eastern (MID) AF: 0.322 AC: 29 AN: 90

European-Non Finnish (NFE) AF: 0.236 AC: 2518 AN: 10680

Other (OTH) AF: 0.228 AC: 355 AN: 1560

GnomAD4 genome AF: 0.271 AC: 33018 AN: 121636 Hom.: 4457 Cov.: 18 AF XY: 0.270 AC XY: 15633 AN XY: 57986

African (AFR) AF: 0.296 AC: 9019 AN: 30446

American (AMR) AF: 0.247 AC: 2876 AN: 11646

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 936 AN: 3064

East Asian (EAS) AF: 0.0480 AC: 191 AN: 3976

South Asian (SAS) AF: 0.325 AC: 1181 AN: 3632

European-Finnish (FIN) AF: 0.191 AC: 1344 AN: 7024

Middle Eastern (MID) AF: 0.333 AC: 78 AN: 234

European-Non Finnish (NFE) AF: 0.282 AC: 16705 AN: 59216

Other (OTH) AF: 0.292 AC: 474 AN: 1622

Alfa AF: 0.0735 Hom.: 77

Bravo AF: 0.257

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.7
DANN	Benign	0.72
PhyloP100		0.31
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: rs1053129; hg19: chr5-79922720;