rs148878316

Variant names:

• chr11-5233045-C-G
• NM_000519.4:c.363G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-5233045-C-G
• chr11-5233045-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000519.4(HBD):​c.363G>C​(p.Lys121Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: HBD NM_000519.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00

Genes affected

HBD (HGNC:4829): (hemoglobin subunit delta) The delta (HBD) and beta (HBB) genes are normally expressed in the adult: two alpha chains plus two beta chains constitute HbA, which in normal adult life comprises about 97% of the total hemoglobin. Two alpha chains plus two delta chains constitute HbA-2, which with HbF comprises the remaining 3% of adult hemoglobin. Five beta-like globin genes are found within a 45 kb cluster on chromosome 11 in the following order: 5'-epsilon--Ggamma--Agamma--delta--beta-3'. Mutations in the delta-globin gene are associated with beta-thalassemia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1392113).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HBD	NM_000519.4	c.363G>C	p.Lys121Asn	missense_variant	Exon 3 of 3	ENST00000650601.1	NP_000510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HBD	ENST00000650601.1	c.363G>C	p.Lys121Asn	missense_variant	Exon 3 of 3		NM_000519.4	ENSP00000497529.1
HBD	ENST00000643122.1	c.363G>C	p.Lys121Asn	missense_variant	Exon 4 of 4			ENSP00000494708.1
HBD	ENST00000417377.1	c.140G>C	p.Arg47Thr	missense_variant	Exon 2 of 2	3		ENSP00000414741.1
HBD	ENST00000292901.7	c.316-247G>C		intron_variant	Intron 2 of 2	3		ENSP00000292901.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461756 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727192

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	12
DANN	Benign	0.95
DEOGEN2	Benign	0.063	T;T;T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.84	.;.;T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Benign	1.6	L;L;L
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.5	.;D;.
REVEL	Uncertain	0.38
Sift	Benign	0.065	.;T;.
Sift4G	Benign	0.13	.;T;.
Polyphen		0.0040	B;B;B
Vest4		0.22
MutPred		0.45		Loss of methylation at K121 (P = 7e-04);Loss of methylation at K121 (P = 7e-04);Loss of methylation at K121 (P = 7e-04);
MVP		0.86
MPC		0.012
ClinPred		0.091	T
GERP RS		-5.0
Varity_R		0.33
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-5254275;